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Supplementary Materials for Clonal selection drives protective memory B cell responses in controlled human malaria infection Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa, Gemma Pidelaserra Martí, Katharina Imkeller, Christian E. Busse, Sumana Chakravarty, B. Kim Lee Sim, Stephen L. Hoffman, Elena A. Levashina, Peter G. Kremsner, Benjamin Mordmüller, Thomas Höfer,* Hedda Wardemann* *Corresponding author. Email: [email protected] (T.H.); [email protected] (H.W.) Published 16 February 2018, Sci. Immunol. 3, eaap8029 (2018) DOI: 10.1126/sciimmunol.aap8029 The PDF file includes: Fig. S1. Anti-PfCSP response. Fig. S2. PfCSP memory B cell Ig gene sequence analysis and antibody function. Fig. S3. Inefficient affinity maturation over repeated Pf exposure. Fig. S4. Influence of GC seeder cell frequencies and antigen complexity (nkey) on clonal evolution within individual GCs. Fig. S5. Avalanche effect over three successive infections in an exemplary system of 10 different GC sites. Fig. S6. Repertoire and Ig gene feature analysis of antibodies from PfCSP memory B cells and plasmablasts. Table S1. Number of sequenced and cloned PfCSP-reactive memory B cell antibodies. Table S2. Number of sequenced plasmablast antibodies. Table S3. Clonally expanded PfCSP-reactive memory B cell clusters. Table S4. Simulation parameters, binding model, GC simulation dynamics. Table S5. PfCSP-reactive memory B cell antibodies with 8amino acidlong KCDR3. Other Supplementary Material for this manuscript includes the following: (available at immunology.sciencemag.org/cgi/content/full/3/20/eaap8029/DC1) Source data (Microsoft Excel format) immunology.sciencemag.org/cgi/content/full/3/20/eaap8029/DC1

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  • Supplementary Materials for

    Clonal selection drives protective memory B cell responses in controlled

    human malaria infection

    Rajagopal Murugan, Lisa Buchauer, Gianna Triller, Cornelia Kreschel, Giulia Costa,

    Gemma Pidelaserra Martí, Katharina Imkeller, Christian E. Busse, Sumana Chakravarty,

    B. Kim Lee Sim, Stephen L. Hoffman, Elena A. Levashina, Peter G. Kremsner,

    Benjamin Mordmüller, Thomas Höfer,* Hedda Wardemann*

    *Corresponding author. Email: [email protected] (T.H.); [email protected] (H.W.)

    Published 16 February 2018, Sci. Immunol. 3, eaap8029 (2018)

    DOI: 10.1126/sciimmunol.aap8029

    The PDF file includes:

    Fig. S1. Anti-PfCSP response.

    Fig. S2. PfCSP memory B cell Ig gene sequence analysis and antibody function.

    Fig. S3. Inefficient affinity maturation over repeated Pf exposure.

    Fig. S4. Influence of GC seeder cell frequencies and antigen complexity (nkey) on

    clonal evolution within individual GCs.

    Fig. S5. Avalanche effect over three successive infections in an exemplary system

    of 10 different GC sites.

    Fig. S6. Repertoire and Ig gene feature analysis of antibodies from PfCSP

    memory B cells and plasmablasts.

    Table S1. Number of sequenced and cloned PfCSP-reactive memory B cell

    antibodies.

    Table S2. Number of sequenced plasmablast antibodies.

    Table S3. Clonally expanded PfCSP-reactive memory B cell clusters.

    Table S4. Simulation parameters, binding model, GC simulation dynamics.

    Table S5. PfCSP-reactive memory B cell antibodies with 8–amino acid–long

    KCDR3.

    Other Supplementary Material for this manuscript includes the following:

    (available at immunology.sciencemag.org/cgi/content/full/3/20/eaap8029/DC1)

    Source data (Microsoft Excel format)

    immunology.sciencemag.org/cgi/content/full/3/20/eaap8029/DC1

  • fig. S1. Anti-PfCSP response. (A) IgM, IgG and IgA anti-PfCSP serum response after

    repeated immunizations at 1:200-dilution for the indicated donors. (B) Flow cytometric

    identification of 7AAD-CD19+ cells with CD27+IgG+, CD27-IgG+ or CD27+IgG- PfCSP

    reactive memory B cells (top) and 7AAD-CD19+CD27+CD38+ plasmablasts (bottom) for

    representative Pf-immunized and non-immunized donors (left) and respective frequency in all

    donors (right) over repeated infections compared to non-infected controls. Red lines indicate

    mean. **P

  • fig. S2. PfCSP memory B cell Ig gene sequence analysis and antibody function. (A and B)

    Mean IGHV SHM count after each infection in PfCSP memory B cells and plasmabasts from

    individual donors (A) and absolute counts (open circles) and mean (red line) in all donors

    pooled for different isotypes (B); *P

  • fig. S3. Inefficient affinity maturation over repeated Pf exposure. NANP5 affinity of

    clonally related recombinant monoclonal PfCSP memory B cell antibodies from the indicated

    cell clusters isolated post Pf immunizations I, II, III or the CHMI (C). Two-tailed Mann-

    Whitney test was performed to test significance. ns: not significant. Data are representative of

    at least two independent experiments.

  • fig. S4. Influence of GC seeder cell frequencies and antigen complexity (nkey) on clonal

    evolution within individual GCs. (A-F) Two exemplary GCs for the indicated GC seeder

    frequency (A, C and E: many vs B, D and F: few) and antigen complexity (nkey =10: A, B; nkey

    =5: C, D; nkey =1: E, F). The clonal composition as cell numbers, with individual clones in

  • different colors (top), and affinities (KD) of the corresponding clones exiting the GC as

    memory B cells (bottom) are represented as function of time. Inset on the top in the panels

    (A-F) indicates affinity of individual memory cells stemming from the GC-dominating clone

    over mutational state.

  • fig. S5. Avalanche effect over three successive in an exemplary

    system of 10 different GC sites. Clonal composition as cell numbers over time is indicated

    for 10 different follicular GC sites that are followed over three successive antigen (Ag)

    exposures. Each clone is represented in a different color.

    infections

  • fig. S6. Repertoire and Ig gene feature analysis of antibodies from PfCSP memory B

    cells and plasmablasts. (A) PfCSP ELISA reactivity and hepatocyte traversal inhibition of Pf

    sporozoites (35) by antibodies cloned from PfCSP memory B cells obtained at day 7 post Pf

    challenge versus total IGHV plus IGKV or IGLV SHM counts. Open circles indicate

    individual antibodies. Dotted lines indicate germline antibodies. 2A10 (red; 35) and mGO53

  • (blue; 50) are shown as positive and negative control, respectively. (B-C) IGHV segments

    family distribution (B) and frequencies of 8-aa-long Ig (KCDR3) (C) in PfCSP memory B

    cells and plasmablasts for individual donors. (D) NANP5 affinity Kd (M) versus Pf sporozoite

    traversal inhibition of antibodies with 8- or 9-aa-long Ig (KCDR3). Data are representative

    of at least two independent experiments. (E) PfCSP ELISA AUC versus total IGHV plus

    IGKV or IGLV SHM counts for memory B cell antibodies (circles) after Pf exposure I-III and

    the CHMI challenge from the indicated donors. Red and blue squares indicate positive (2A10;

    35) and negative (mGO53; 50) controls. Data in (A), (E), and (D) are representative of at least

    two independent experiments.

  • table S1. Number of sequenced and cloned PfCSP memory B cell antibodies.

    donors I II III I II IIIT2_017 29 9 12 10 6 12T2_026 17 13 31 4 3 9T2_035 58 18 32 8 4 10T2_042 2 12 52 1 8 29T2_051 29 62 90 15 22 28T2_052 5 6 1 0 0 0T2_071 1 22 124 1 16 33T2_072 17 53 95 7 23 37T2_073 NA 86 142 NA 29 51

    table S2. Number of sequenced plasmablast antibodies.

    donors I II IIIT2_017 58 64 38T2_026 73 229 241T2_035 181 316 250T2_042 38 123 103T2_051 165 211 262T2_052 246 226 23T2_071 72 283 217T2_072 137 109 191T2_073 NA 209 147

    *paired functional IGH and IGK/IGL genesNA: Not available

    Sequences*

    CSP memory

    Plasmablast

    Antibodies clonedAntibody sequences*

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_017 clr02 II 1-46 3-9 4 13 19 IGHM lambda 2-8 2 10 4 CSP-CD27+CD38+T2_017 clr02 III 1-46 3-9 4 13 19 IGHM lambda 2-8 2 10 4 CSP+CD27+CD38-T2_017 clr16 I 4-4 ND 4 15 8 IGHM kappa 2D-29 2 9 8 CSP+CD27+CD38-T2_017 clr16 C 4-4 ND 4 15 7 IGHM kappa 2D-29 2 9 10 CSP+CD27+CD38-T2_017 clr19 I 4-59 6-13 6 19 4 IGHG2 kappa 3-20 1 9 3 CSP-CD27+CD38+T2_017 clr19 I 4-59 6-13 6 19 4 IGHG2 kappa 3-20 1 9 3 CSP+CD27+CD38+T2_017 clr19 I 4-59 6-13 6 19 4 IGHG2 kappa 3-20 1 9 3 CSP-CD27+CD38+T2_017 clr19 I 4-59 6-13 6 19 4 IGHG2 kappa 3-20 1 9 3 CSP-CD27+CD38+T2_017 clr19 I 4-59 6-13 6 19 4 IGHG2 kappa 3-20 1 9 3 CSP+CD27+CD38+T2_026 clr03 I 1-8 5/OR15-5a 4 4 14 IGHG2 kappa 2D-29 1 9 18 CSP+CD27+CD38-T2_026 clr03 C 1-8 5/OR15-5a 4 4 9 IGHG2 kappa 2D-29 1 9 12 CSP+CD27+CD38-T2_026 clr08 C 4-31 1-26 4 14 9 IGHM kappa 1-39 5 9 5 CSP-CD27+CD38+T2_026 clr08 C 4-31 1-26 4 14 12 IGHM kappa 1-39 5 9 7 CSP-CD27+CD38+T2_026 clr08 C 4-31 1-26 4 14 9 IGHA2 kappa 1-39 5 9 6 CSP+CD27+CD38+T2_026 clr08 C 4-31 1-26 4 14 12 IGHA2 kappa 1-39 5 9 9 CSP-CD27+CD38+T2_026 clr08 C 4-31 1-26 4 14 11 IGHA2 kappa 1-39 5 9 9 CSP-CD27+CD38+T2_026 clr08 C 4-31 1-26 4 14 12 IGHA2 kappa 1-39 5 9 9 CSP-CD27+CD38+T2_026 clr12 I 4-39 2-21 4 13 14 IGHA2 lambda 3-21 2 11 14 CSP+CD27+CD38+T2_026 clr12 I 4-39 2-21 4 13 18 IGHA2 lambda 3-21 2 11 14 CSP-CD27+CD38+T2_026 clr17 III 1-69 3-22 4 13 2 IGHM kappa 3-20 2 9 0 CSP+CD27+CD38-T2_026 clr17 C 1-69 3-22 4 13 21 IGHM kappa 3-20 2 9 7 CSP+CD27+CD38-T2_026 clr21 I 1-8 3-10 4 15 3 IGHG2 lambda 2-14 3 9 7 CSP-CD27+CD38+T2_026 clr21 C 1-8 3-10 4 15 0 IGHG2 lambda 2-14 2 9 6 CSP+CD27+CD38-T2_026 clr28 III 3-33 5-24 4 18 10 IGHA1 kappa 1-33 4 8 15 CSP-CD27+CD38+T2_026 clr28 C 3-33 3-10 4 18 5 IGHM kappa 1-33 4 8 8 CSP+CD27+CD38-T2_026 clr32 C 3-72 4-17 4 11 16 IGHG2 kappa 1-39 4 9 25 CSP+CD27+CD38-T2_026 clr32 C 3-72 4-17 4 11 8 IGHA2 kappa 1-39 4 9 10 CSP-CD27+CD38+T2_026 clr39 I 4-39 3-10 4 17 15 IGHA1 lambda 6-57 2 9 19 CSP-CD27+CD38+T2_026 clr39 C 4-39 3-10 4 17 23 IGHA1 lambda 6-57 2 9 19 CSP+CD27+CD38+T2_026 clr42 II 4-4 1-14 5 15 14 IGHG3 kappa 1-39 2 10 11 CSP+CD27+CD38-T2_026 clr42 C 4-4 1-14 5 15 11 IGHG3 kappa 1-39 2 10 7 CSP+CD27+CD38-T2_026 clr43 C 4-4 ND 5 16 29 IGHG2 kappa 3-20 2 11 20 CSP+CD27+CD38+T2_026 clr43 C 4-4 ND 5 16 20 IGHG2 kappa 3-20 2 11 14 CSP-CD27+CD38+T2_035 clr16 I 3-30-3 ND 4 10 22 IGHG1 lambda 1-44 3 11 8 CSP+CD27+CD38+T2_035 clr16 I 3-30-3 7-27 4 10 17 IGHA1 lambda 1-44 3 11 11 CSP-CD27+CD38+T2_035 clr16 I 3-30-3 ND 4 10 21 IGHG1 lambda 1-44 3 11 8 CSP-CD27+CD38+T2_035 clr16 I 3-30-3 ND 4 10 15 IGHG1 lambda 1-44 3 11 10 CSP-CD27+CD38+T2_035 clr16 I 3-30-3 7-27 4 10 21 IGHA1 lambda 1-44 3 11 7 CSP-CD27+CD38+T2_035 clr23 I 3-64 3-22 4 17 25 IGHA2 kappa 1-9 3 10 18 CSP+CD27+CD38+T2_035 clr23 I 3-64 3-22 4 17 33 IGHA1 kappa 1-9 3 10 19 CSP-CD27+CD38+T2_035 clr28 I 3-7 7-27 6 15 17 IGHA2 kappa 3-20 1 9 10 CSP+CD27+CD38+T2_035 clr28 I 3-7 7-27 6 15 11 IGHG2 kappa 3-20 1 9 9 CSP-CD27+CD38+T2_035 clr28 I 3-7 7-27 6 15 15 IGHA2 kappa 3-20 1 9 7 CSP-CD27+CD38+T2_035 clr31 I 3-7 3-10 6 18 18 IGHA2 kappa 3-20 1 9 9 CSP+CD27+CD38+T2_035 clr31 I 3-7 3-10 6 18 19 IGHA2 kappa 3-20 1 9 19 CSP-CD27+CD38+T2_035 clr31 I 3-7 ND 6 18 15 IGHA2 kappa 3-20 1 9 13 CSP-CD27+CD38+T2_035 clr33 I 3-74 ND 3 15 12 IGHA1 kappa 2-28 2 9 13 CSP+CD27+CD38+T2_035 clr33 I 3-74 2-2 3 15 24 IGHA2 kappa 2-28 2 9 13 CSP+CD27+CD38+T2_035 clr33 I 3-74 2-2 3 15 23 IGHA2 kappa 2-28 2 9 13 CSP-CD27+CD38+T2_035 clr33 I 3-74 ND 3 15 17 IGHG2 kappa 2-28 2 9 5 CSP-CD27+CD38+T2_035 clr36 I 3-74 ND 2 15 20 IGHM lambda 2-23 1 10 11 CSP+CD27+CD38-T2_035 clr36 II 3-74 ND 2 15 23 IGHA2 lambda 2-23 1 10 6 CSP-CD27+CD38+T2_035 clr47 I 1-46 ND 4 15 19 IGHM kappa 1-6 1 9 3 CSP+CD27+CD38-T2_035 clr47 III 1-46 ND 4 15 19 IGHG2 kappa 1-6 1 9 9 CSP-CD27+CD38+T2_035 clr65 I 3-64D ND 4 14 21 IGHA1 kappa 2-30 2 9 6 CSP+CD27+CD38+

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_035 clr65 I 3-64D ND 4 14 16 IGHA1 kappa 2-30 2 9 8 CSP-CD27+CD38+T2_035 clr79 III 4-39 ND 4 11 35 IGHG1 lambda 2-8 3 10 23 CSP+CD27+CD38-T2_035 clr79 C 4-39 ND 4 11 24 IGHA1 lambda 2-8 3 10 14 CSP+CD27+CD38-T2_035 clr81 III 4-59 5-24 3 16 17 IGHM lambda 1-51 3 9 13 CSP+CD27+CD38-T2_035 clr81 C 4-59 5-24 3 16 17 IGHM lambda 1-51 3 9 13 CSP+CD27+CD38-T2_035 clr85 II 4-59 2-2 4 19 15 IGHA2 lambda 2-8 3 10 8 CSP-CD27+CD38+T2_035 clr85 II 4-59 2-2 4 19 30 IGHA2 lambda 2-8 3 10 12 CSP+CD27+CD38-T2_035 clr85 C 4-59 2-2 4 19 25 IGHA2 lambda 2-8 3 11 13 CSP-CD27+CD38+T2_042 clr07 II 3-23 6-19 4 15 5 IGHM lambda 2-14 2 10 4 CSP-CD27+CD38+T2_042 clr07 III 3-23 6-19 4 15 8 IGHM lambda 2-14 2 10 8 CSP+CD27+CD38-T2_042 clr07 III 3-23 6-19 4 15 6 IGHM lambda 2-14 2 10 5 CSP+CD27+CD38+T2_042 clr07 III 3-23 6-19 4 15 6 IGHM lambda 2-14 2 10 2 CSP+CD27+CD38-T2_042 clr07 III 3-23 6-19 4 15 10 IGHM lambda 2-14 2 10 9 CSP+CD27+CD38-T2_042 clr07 III 3-23 6-19 4 15 6 IGHM lambda 2-14 2 10 2 CSP+CD27+CD38-T2_042 clr07 III 3-23 6-19 4 15 9 IGHM lambda 2-14 2 10 13 CSP-CD27+CD38+T2_042 clr07 C 3-23 6-19 4 15 10 IGHM lambda 2-14 2 10 9 CSP+CD27+CD38-T2_042 clr07 C 3-23 6-19 4 15 8 IGHM lambda 2-14 2 10 8 CSP+CD27+CD38-T2_042 clr07 C 3-23 6-19 4 15 11 IGHM lambda 2-14 2 10 6 CSP+CD27+CD38-T2_042 clr10 III 3-30 2-8 4 20 8 IGHM kappa 3-15 1 9 4 CSP+CD27+CD38+T2_042 clr10 III 3-30 2-8 4 20 8 IGHM kappa 3-15 1 9 4 CSP+CD27+CD38+T2_042 clr10 III 3-30 2-8 4 20 8 IGHM kappa 3-15 1 9 4 CSP+CD27+CD38-T2_042 clr10 III 3-30 2-8 4 20 8 IGHM kappa 3-15 1 9 4 CSP+CD27+CD38-T2_042 clr10 III 3-30 2-8 4 20 8 IGHM kappa 3-15 1 9 4 CSP+CD27+CD38+T2_042 clr10 III 3-30 2-8 4 20 8 IGHM kappa 3-15 1 9 4 CSP+CD27+CD38-T2_042 clr11 II 3-30 1-1 4 15 7 IGHM kappa 3-15 1 9 6 CSP+CD27+CD38-T2_042 clr11 III 3-30 1-1 4 15 7 IGHM kappa 3-15 1 9 6 CSP+CD27+CD38-T2_042 clr11 III 3-30 1-1 4 15 7 IGHM kappa 3-15 1 9 6 CSP-CD27+CD38+T2_042 clr11 III 3-30 1-1 4 15 7 IGHM kappa 3-15 1 9 6 CSP+CD27+CD38+T2_042 clr11 III 3-30 1-1 4 15 5 IGHM kappa 3-15 1 9 1 CSP+CD27+CD38+T2_042 clr11 III 3-30 1-1 4 15 7 IGHM kappa 3-15 1 9 6 CSP+CD27+CD38-T2_042 clr11 III 3-30 1-1 4 15 7 IGHM kappa 3-15 1 9 6 CSP+CD27+CD38+T2_042 clr12 III 3-30 4/OR15-4a 3 20 8 IGHM kappa 3-15 2 9 3 CSP+CD27+CD38-T2_042 clr12 III 3-30 4/OR15-4a 3 20 7 IGHM kappa 3-15 2 9 3 CSP-CD27+CD38+T2_042 clr12 III 3-30 4/OR15-4a 3 20 8 IGHM kappa 3-15 2 9 3 CSP-CD27+CD38+T2_042 clr14 III 3-30 1-26 4 13 1 IGHM lambda 2-14 2 10 1 CSP-CD27+CD38+T2_042 clr14 III 3-30 1-26 4 13 1 IGHM lambda 2-14 2 10 1 CSP+CD27+CD38+T2_042 clr16 III 3-33 6-19 4 12 0 IGHM kappa 2-24 1 8 0 CSP+CD27+CD38+T2_042 clr16 C 3-33 6-19 4 12 2 IGHM kappa 2-24 1 8 0 CSP+CD27+CD38-T2_042 clr19 III 3-33 7-27 4 14 16 IGHM kappa 2-24 1 9 7 CSP+CD27+CD38+T2_042 clr19 III 3-33 7-27 4 14 9 IGHM kappa 2-24 1 9 7 CSP+CD27+CD38-T2_042 clr20 III 3-33 1-7 4 15 12 IGHM kappa 2-24 1 9 5 CSP+CD27+CD38-T2_042 clr20 III 3-33 1-7 4 15 13 IGHM kappa 2-24 1 9 5 CSP+CD27+CD38-T2_042 clr22 C 3-7 6-19 3 13 10 IGHA2 kappa 4-1 3 9 6 CSP-CD27+CD38+T2_042 clr22 C 3-7 6-19 3 13 10 IGHA2 kappa 4-1 3 9 6 CSP+CD27+CD38+T2_042 clr23 C 3-7 ND 4 6 26 IGHA2 kappa 1-33 5 8 9 CSP-CD27+CD38+T2_042 clr23 C 3-7 ND 4 6 26 IGHM kappa 1-33 5 8 13 CSP+CD27+CD38+T2_042 clr31 III 3-21 2-15 4 20 15 IGHM lambda 2-14 2 11 3 CSP+CD27+CD38+T2_042 clr31 III 3-21 2-15 4 20 24 IGHA2 lambda 2-14 3 11 12 CSP-CD27+CD38+T2_051 clr01 II 1-2 ND 4 15 12 IGHM lambda 1-51 2 11 7 CSP-CD27+CD38+T2_051 clr01 III 1-2 ND 4 15 25 IGHM lambda 1-51 2 11 25 CSP+CD27+CD38-T2_051 clr02 II 1-3 ND 4 13 17 IGHM lambda 1-47 3 12 7 CSP-CD27+CD38+T2_051 clr02 II 1-3 ND 4 13 12 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38+T2_051 clr02 II 1-3 6-13 4 13 6 IGHM lambda 1-47 3 12 6 CSP-CD27+CD38+T2_051 clr02 II 1-3 6-13 4 13 8 IGHM lambda 1-47 3 12 6 CSP+CD27+CD38+T2_051 clr02 II 1-3 6-13 4 13 6 IGHM lambda 1-47 3 12 7 CSP+CD27+CD38-

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_051 clr02 II 1-3 6-13 4 13 10 IGHM lambda 1-47 3 12 5 CSP+CD27+CD38-T2_051 clr02 II 1-3 6-13 4 13 16 IGHM lambda 1-47 3 12 6 CSP+CD27+CD38-T2_051 clr02 II 1-3 6-13 4 13 8 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38+T2_051 clr02 II 1-3 6-13 4 13 0 IGHM lambda 1-47 3 12 6 CSP+CD27+CD38-T2_051 clr02 II 1-3 6-13 4 13 8 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr02 II 1-3 6-13 4 13 8 IGHM lambda 1-47 3 12 2 CSP-CD27+CD38+T2_051 clr02 III 1-3 6-13 4 13 4 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 11 IGHM lambda 1-47 3 12 5 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 12 IGHM lambda 1-47 3 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 17 IGHM lambda 1-47 2 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 9 IGHM lambda 1-47 3 12 7 CSP+CD27+CD38-T2_051 clr02 III 1-3 ND 4 13 11 IGHM lambda 1-47 2 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 ND 4 13 15 IGHM lambda 1-47 3 12 3 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 11 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 14 IGHG1 lambda 1-47 3 12 9 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 14 IGHM lambda 1-47 3 12 6 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 15 IGHM lambda 1-47 3 12 7 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 11 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 18 IGHM lambda 1-47 3 12 7 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 13 IGHM lambda 1-47 3 12 9 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 11 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 14 IGHM lambda 1-47 3 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 ND 4 13 11 IGHM lambda 1-47 2 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 14 IGHM lambda 1-47 2 12 5 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 11 IGHM lambda 1-47 3 12 9 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 15 IGHM lambda 1-47 2 12 6 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 11 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 14 IGHM lambda 1-47 3 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 ND 4 13 14 IGHG1 lambda 1-47 3 12 6 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 16 IGHM lambda 1-47 3 12 8 CSP+CD27+CD38-T2_051 clr02 III 1-3 6-13 4 13 18 IGHM lambda 1-47 3 12 7 CSP+CD27+CD38-T2_051 clr02 C 1-3 6-13 4 13 10 IGHM lambda 1-47 3 12 4 CSP+CD27+CD38-T2_051 clr16 I 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38+T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP-CD27+CD38+T2_051 clr16 II 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr16 III 4-39 6-19 3 15 8 IGHM lambda 1-40 1 12 3 CSP+CD27+CD38-T2_051 clr25 II 3-30 2-15 4 13 14 IGHM lambda 1-47 3 11 12 CSP+CD27+CD38-T2_051 clr25 III 3-30 2-15 4 13 9 IGHM lambda 1-47 3 11 11 CSP+CD27+CD38-T2_051 clr25 III 3-30 2-15 4 13 14 IGHM lambda 1-47 3 11 12 CSP+CD27+CD38-T2_051 clr25 C 3-30 2-15 4 13 10 IGHM lambda 1-47 3 11 15 CSP+CD27+CD38-T2_051 clr29 I 3-30 3-22 4 15 22 IGHG1 lambda 2-11 1 10 11 CSP-CD27+CD38+T2_051 clr29 II 3-30 3-22 4 15 22 IGHG1 lambda 2-11 1 10 11 CSP+CD27+CD38-T2_051 clr33 II 3-66 5-24 4 17 26 IGHA1 kappa 3-11 1 9 10 CSP+CD27+CD38-T2_051 clr33 C 3-66 5-24 4 17 24 IGHM kappa 3-11 1 9 12 CSP-CD27+CD38+T2_051 clr34 I 3-74 3-10 4 16 20 IGHG2 lambda 2-8 2 9 11 CSP-CD27+CD38+T2_051 clr34 C 3-74 3-10 4 16 20 IGHG2 lambda 2-8 2 9 12 CSP+CD27+CD38+T2_071 clr02 II 1-2 2-15 4 13 6 IGHM kappa 2-28 2 8 5 CSP+CD27+CD38-T2_071 clr02 II 1-2 2-15 4 13 6 IGHM kappa 2-28 2 8 5 CSP+CD27+CD38+T2_071 clr02 II 1-2 2-15 4 13 6 IGHG1 kappa 2-28 2 8 5 CSP+CD27+CD38-T2_071 clr02 III 1-2 2-15 4 13 6 IGHG1 kappa 2-28 2 8 5 CSP-CD27+CD38+T2_071 clr02 III 1-2 2-15 4 13 6 IGHM kappa 2-28 2 8 5 CSP+CD27+CD38+T2_071 clr02 III 1-2 2-15 4 13 6 IGHM kappa 2-28 2 8 5 CSP+CD27+CD38-T2_071 clr02 III 1-2 2-15 4 13 6 IGHM kappa 2-28 2 8 5 CSP+CD27+CD38-T2_071 clr02 III 1-2 2-15 4 13 6 IGHG1 kappa 2-28 2 8 5 CSP-CD27+CD38+T2_071 clr08 III 3-15 ND 4 7 12 IGHG1 kappa 2-30 1 10 2 CSP+CD27+CD38-T2_071 clr08 III 3-15 ND 4 7 12 IGHG1 kappa 2-30 1 10 1 CSP+CD27+CD38-T2_071 clr08 III 3-15 ND 4 7 11 IGHM kappa 2-30 1 10 1 CSP+CD27+CD38-T2_071 clr08 III 3-15 ND 4 7 12 IGHM kappa 2-30 1 10 1 CSP+CD27+CD38+T2_071 clr08 C 3-15 ND 4 7 12 IGHM kappa 2-30 1 10 2 CSP+CD27+CD38+T2_071 clr08 C 3-15 ND 4 7 12 IGHM kappa 2-30 1 10 2 CSP+CD27+CD38-T2_071 clr08 C 3-15 ND 4 7 12 IGHM kappa 2-30 1 10 2 CSP+CD27+CD38-T2_071 clr14 II 3-23 6-19 4 14 13 IGHM lambda 1-47 1 11 7 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHG3 lambda 1-47 2 11 0 CSP-CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHG3 lambda 1-47 2 11 0 CSP-CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP-CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 15 IGHM lambda 1-47 1 11 7 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 4 IGHM lambda 1-47 2 11 3 CSP+CD27+CD38+

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHG1 lambda 1-47 2 11 0 CSP-CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHG3 lambda 1-47 2 11 0 CSP-CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP-CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 C 3-23 6-19 4 14 3 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_071 clr14 C 3-23 6-19 4 14 2 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr14 C 3-23 6-19 4 14 2 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_071 clr16 III 3-23 6-13 3 15 13 IGHM kappa 3-20 1 8 4 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 13 IGHM kappa 3-20 1 8 4 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 13 IGHM kappa 3-20 1 8 4 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 13 IGHM kappa 3-20 1 8 4 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 13 IGHM kappa 3-20 1 8 4 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 15 IGHM kappa 3-20 1 8 5 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 13 IGHM kappa 3-20 1 8 4 CSP+CD27+CD38-T2_071 clr16 C 3-23 6-13 3 15 14 IGHM kappa 3-20 1 8 5 CSP+CD27+CD38-T2_071 clr18 C 3-23 5-24 4 15 23 IGHA2 kappa 4-1 1 8 8 CSP-CD27+CD38+T2_071 clr18 C 3-23 ND 4 15 27 IGHA1 kappa 4-1 1 8 9 CSP-CD27+CD38+T2_071 clr18 C 3-23 5-24 4 15 23 IGHA2 kappa 4-1 1 8 8 CSP-CD27+CD38+T2_071 clr18 C 3-23 5-24 4 15 23 IGHA2 kappa 4-1 1 8 8 CSP+CD27+CD38+T2_071 clr22 II 3-30-3 ND 4 15 38 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 ND 4 15 38 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 35 IGHA2 kappa 1-5 1 9 12 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30 ND 4 15 42 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 35 IGHA2 kappa 1-5 1 9 12 CSP-CD27+CD38+T2_071 clr22 II 3-30 ND 4 15 38 IGHA2 kappa 1-5 1 9 16 CSP-CD27+CD38+T2_071 clr22 II 3-30 ND 4 15 42 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30 ND 4 15 42 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 42 IGHA2 kappa 1-5 1 9 21 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30 ND 4 15 42 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30 NN 4 15 42 IGHA2 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 19 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 43 IGHA2 kappa 1-5 1 9 14 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 39 IGHM kappa 1-5 1 9 15 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 ND 4 15 38 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 41 IGHA2 kappa 1-5 1 9 19 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30 ND 4 15 42 IGHA1 kappa 1-5 1 9 11 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 38 IGHA2 kappa 1-5 1 9 8 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 13 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 41 IGHA2 kappa 1-5 1 9 20 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 19 CSP-CD27+CD38+

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_071 clr22 II 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 12 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 35 IGHM kappa 1-5 1 9 12 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 2-2 4 15 39 IGHA2 kappa 1-5 1 9 15 CSP-CD27+CD38+T2_071 clr22 II 3-30-3 ND 4 15 39 IGHA2 kappa 1-5 1 9 10 CSP-CD27+CD38+T2_071 clr22 C 3-30-3 2-2 4 15 40 IGHA2 kappa 1-5 1 9 11 CSP+CD27-CD38-T2_071 clr25 III 3-30 4-17 3 14 3 IGHM kappa 3-20 2 9 1 CSP+CD27+CD38-T2_071 clr25 III 3-30 4-17 3 14 3 IGHM kappa 3-20 2 9 1 CSP-CD27+CD38+T2_071 clr25 III 3-30 4-17 3 14 3 IGHM kappa 3-20 2 9 1 CSP+CD27+CD38+T2_071 clr25 III 3-30 4-17 3 14 3 IGHM kappa 3-20 2 9 1 CSP+CD27+CD38-T2_071 clr25 III 3-30 4-17 3 14 6 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38+T2_071 clr25 III 3-30 4-17 3 14 5 IGHM kappa 3-20 2 9 1 CSP+CD27+CD38+T2_071 clr25 III 3-30 4-17 3 14 3 IGHG3 kappa 3-20 2 9 1 CSP-CD27+CD38+T2_071 clr25 III 3-30 4-17 3 14 4 IGHG1 kappa 3-20 2 9 1 CSP+CD27+CD38+T2_071 clr25 C 3-30 4-17 3 14 3 IGHM kappa 3-20 2 9 1 CSP+CD27+CD38+T2_071 clr26 II 3-30 2-2 4 17 7 IGHM lambda 3-21 3 11 5 CSP+CD27+CD38-T2_071 clr26 III 3-30 2-2 4 17 7 IGHM lambda 3-21 3 11 5 CSP+CD27+CD38-T2_071 clr27 III 3-33 2-15 4 17 0 IGHG1 kappa 1-5 1 8 2 CSP+CD27+CD38-T2_071 clr27 C 3-33 2-15 4 17 0 IGHG1 kappa 1-5 1 8 2 CSP-CD27+CD38+T2_071 clr29 III 3-33 5-24 6 10 5 IGHG1 kappa 2-24 2 8 2 CSP+CD27+CD38-T2_071 clr29 C 3-33 5-24 6 10 5 IGHM kappa 2-24 2 8 2 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP-CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38-T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr30 III 3-33 1-7 4 12 9 IGHM kappa 2-24 2 8 3 CSP+CD27+CD38+T2_071 clr31 III 3-33 1-1 5 11 2 IGHM kappa 3-11 2 8 2 CSP+CD27+CD38+T2_071 clr31 III 3-33 1-1 5 11 2 IGHM kappa 3-11 2 8 3 CSP+CD27+CD38-T2_071 clr31 III 3-33 1-1 5 11 2 IGHM kappa 3-11 2 8 2 CSP+CD27+CD38-T2_071 clr32 III 3-33 2-21 4 13 8 IGHA1 kappa 3-11 1 9 5 CSP+CD27+CD38-T2_071 clr32 III 3-33 2-21 4 13 8 IGHA1 kappa 3-11 1 9 5 CSP+CD27+CD38-T2_071 clr32 III 3-33 2-21 4 13 1 IGHM kappa 3-11 1 9 1 CSP+CD27+CD38-T2_071 clr32 C 3-33 2-21 4 13 1 IGHM kappa 3-11 1 9 1 CSP+CD27+CD38-T2_071 clr33 II 3-33 4-11 6 13 14 IGHM kappa 3-20 2 8 5 CSP+CD27+CD38+T2_071 clr33 II 3-33 4-11 6 13 5 IGHM kappa 3-20 2 8 1 CSP+CD27+CD38+T2_071 clr33 II 3-33 4-11 6 13 5 IGHM kappa 3-20 2 8 1 CSP+CD27+CD38+T2_071 clr33 II 3-33 4-11 6 13 8 IGHM kappa 3-20 2 8 1 CSP+CD27+CD38+T2_071 clr33 II 3-33 4-11 6 13 14 IGHM kappa 3-20 2 8 5 CSP+CD27+CD38-T2_071 clr33 II 3-33 4-11 6 13 8 IGHM kappa 3-20 2 8 3 CSP+CD27+CD38+T2_071 clr33 III 3-33 4-11 6 13 9 IGHM kappa 3-20 2 8 2 CSP+CD27+CD38+T2_071 clr33 III 3-33 4-11 6 13 10 IGHM kappa 3-20 2 8 3 CSP+CD27+CD38+T2_071 clr33 III 3-33 4-11 6 13 7 IGHM kappa 3-20 2 8 5 CSP+CD27+CD38-T2_071 clr33 III 3-33 4-11 6 13 7 IGHM kappa 3-20 2 8 2 CSP+CD27+CD38+

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_071 clr33 III 3-33 4-11 6 13 10 IGHM kappa 3-20 2 8 3 CSP+CD27+CD38+T2_071 clr33 III 3-33 4-11 6 13 7 IGHM kappa 3-20 2 8 2 CSP+CD27+CD38+T2_071 clr33 III 3-33 4-11 6 13 7 IGHM kappa 3-20 2 8 2 CSP+CD27+CD38+T2_071 clr33 III 3-33 4-11 6 13 7 IGHM kappa 3-20 2 8 2 CSP+CD27+CD38-T2_071 clr33 C 3-33 4-11 6 13 9 IGHM kappa 3-20 2 8 3 CSP-CD27+CD38+T2_071 clr34 III 3-33 4-11 4 14 2 IGHM kappa 3-20 1 9 0 CSP+CD27+CD38-T2_071 clr34 III 3-33 4-11 4 14 0 IGHM kappa 3-20 1 9 0 CSP+CD27+CD38+T2_071 clr34 C 3-33 4-11 4 14 1 IGHG1 kappa 3-20 1 9 2 CSP+CD27+CD38+T2_071 clr36 III 3-48 4-23 3 16 10 IGHM kappa 1-17 4 9 1 CSP+CD27+CD38+T2_071 clr36 III 3-48 ND 3 16 12 IGHG1 kappa 1-17 4 9 2 CSP-CD27+CD38+T2_071 clr36 III 3-48 ND 3 16 8 IGHM kappa 1-17 4 9 3 CSP+CD27+CD38-T2_071 clr36 III 3-48 4-23 3 16 10 IGHM kappa 1-17 4 9 1 CSP+CD27+CD38-T2_071 clr36 III 3-48 ND 3 16 12 IGHG1 kappa 1-17 4 7 5 CSP-CD27+CD38+T2_071 clr36 III 3-48 4-23 3 16 10 IGHM kappa 1-17 4 9 1 CSP+CD27+CD38+T2_071 clr36 III 3-48 4-23 3 16 10 IGHG1 kappa 1-17 4 9 1 CSP-CD27+CD38+T2_071 clr36 III 3-48 4-23 3 16 12 IGHA1 kappa 1-17 4 9 6 CSP+CD27+CD38-T2_071 clr36 C 3-48 4-23 3 16 10 IGHG1 kappa 1-17 4 9 1 CSP-CD27+CD38+T2_071 clr36 C 3-48 4-23 3 16 10 IGHM kappa 1-17 4 9 1 CSP+CD27+CD38-T2_071 clr37 III 3-49 ND 4 13 0 IGHM kappa 2D-29 1 9 0 CSP+CD27+CD38-T2_071 clr37 C 3-49 ND 4 13 3 IGHM kappa 2D-29 1 9 3 CSP+CD27+CD38-T2_071 clr38 III 3-49 6-13 4 13 1 IGHM kappa 3-20 1 9 0 CSP+CD27+CD38-T2_071 clr38 C 3-49 6-13 4 13 5 IGHG1 kappa 3-20 1 9 1 CSP+CD27+CD38-T2_071 clr38 C 3-49 6-13 4 13 6 IGHM kappa 3-20 1 9 3 CSP+CD27+CD38-T2_071 clr42 II 3-7 ND 4 11 6 IGHM lambda 1-51 2 11 6 CSP+CD27+CD38-T2_071 clr42 II 3-7 3-3 3 11 7 IGHM lambda 1-51 2 11 2 CSP+CD27+CD38-T2_071 clr42 III 3-7 3-3 3 11 7 IGHM lambda 1-51 2 11 3 CSP+CD27+CD38-T2_071 clr57 III 4-4 2-15 6 13 1 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr57 III 4-4 2-15 6 13 1 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr57 III 4-4 2-15 6 13 1 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr57 III 4-4 2-15 6 13 3 IGHM kappa 3-20 2 9 1 CSP-CD27+CD38+T2_071 clr57 C 4-4 2-15 6 13 1 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr57 C 4-4 ND 6 13 10 IGHM kappa 3-20 2 9 7 CSP+CD27+CD38-T2_071 clr57 C 4-4 2-15 6 13 1 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr57 C 4-4 2-15 6 13 2 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr57 C 4-4 2-15 6 13 1 IGHM kappa 3-20 2 9 2 CSP+CD27+CD38-T2_071 clr68 II 3-15 4-11 4 11 7 IGHM kappa 2-28 1 9 0 CSP+CD27+CD38-T2_071 clr68 C 3-15 4-11 4 11 7 IGHM kappa 2-28 1 9 0 CSP+CD27+CD38-T2_071 clr75 II 3-33 ND 4 12 1 IGHM lambda 2-14 1 11 3 CSP+CD27+CD38-T2_071 clr75 III 3-33 ND 4 12 4 IGHM lambda 2-14 2 10 3 CSP+CD27+CD38-T2_071 clr81 III 3-49 4-23 4 13 0 IGHG2 kappa 3-20 1 9 0 CSP+CD27+CD38+T2_071 clr81 C 3-49 4-23 4 13 3 IGHM kappa 3-20 1 9 3 CSP+CD27+CD38+T2_072 clr01 III 1-2 ND 3 14 1 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHG1 lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 1 IGHM lambda 2-23 2 12 1 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 III 1-2 4-23 3 14 2 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr01 C 1-2 4-23 3 14 0 IGHM lambda 2-23 2 12 0 CSP+CD27+CD38-T2_072 clr07 II 3-30-3 1-26 3 15 4 IGHM kappa 3-11 4 9 0 CSP+CD27+CD38-T2_072 clr07 II 3-30-3 1-26 3 15 7 IGHM kappa 3-11 4 9 0 CSP+CD27+CD38-

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_072 clr07 II 3-30-3 1-26 3 15 2 IGHM kappa 3-11 4 9 1 CSP+CD27+CD38+T2_072 clr07 II 3-30-3 1-26 3 15 7 IGHM kappa 3-11 4 9 1 CSP+CD27+CD38-T2_072 clr07 II 3-30-3 1-26 3 15 0 IGHM kappa 3-11 4 9 1 CSP+CD27+CD38-T2_072 clr07 II 3-30-3 1-26 3 15 7 IGHM kappa 3-11 4 9 0 CSP+CD27+CD38-T2_072 clr07 II 3-30-3 1-26 3 15 4 IGHM kappa 3-11 4 9 0 CSP+CD27+CD38+T2_072 clr08 II 3-30-3 1-14 3 15 8 IGHM kappa 3-11 1 9 0 CSP+CD27+CD38+T2_072 clr08 III 3-30-3 1-14 3 15 5 IGHM kappa 3-11 1 9 1 CSP+CD27+CD38-T2_072 clr09 I 3-30-3 6-19 4 16 2 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38-T2_072 clr09 II 3-30-3 6-19 4 16 3 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38+T2_072 clr09 II 3-30-3 6-19 4 16 1 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38-T2_072 clr09 II 3-30-3 6-19 4 16 2 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38+T2_072 clr09 II 3-30-3 6-19 4 16 3 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38-T2_072 clr09 III 3-30-3 6-19 4 16 3 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38-T2_072 clr09 III 3-30-3 6-19 4 16 3 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38-T2_072 clr09 III 3-30-3 6-19 4 16 2 IGHM lambda 4-69 3 9 2 CSP+CD27+CD38-T2_072 clr11 II 3-30 ND 5 19 6 IGHM lambda 9-49 1 13 4 CSP-CD27+CD38+T2_072 clr11 II 3-30 2-15 4 19 2 IGHM lambda 9-49 1 13 2 CSP+CD27+CD38-T2_072 clr11 II 3-30 ND 5 19 8 IGHM lambda 9-49 1 13 4 CSP+CD27+CD38-T2_072 clr11 II 3-30 ND 4 19 11 IGHM lambda 9-49 1 13 3 CSP+CD27+CD38+T2_072 clr11 III 3-30 2-15 4 19 5 IGHM lambda 9-49 1 13 3 CSP+CD27+CD38-T2_072 clr11 III 3-30 2-15 4 19 5 IGHM lambda 9-49 1 13 1 CSP+CD27+CD38-T2_072 clr12 III 3-33 2-15 2 17 0 IGHG1 kappa 4-1 1 9 0 CSP+CD27-CD38-T2_072 clr12 III 3-33 2-15 2 17 0 IGHM kappa 4-1 1 9 0 CSP+CD27+CD38-T2_072 clr13 III 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38-T2_072 clr13 III 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38+T2_072 clr13 III 3-33 4-17 3 20 3 IGHG1 kappa 1-5 3 8 1 CSP+CD27+CD38-T2_072 clr13 III 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38-T2_072 clr13 III 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38-T2_072 clr13 III 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38-T2_072 clr13 III 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38-T2_072 clr13 C 3-33 4-17 3 20 0 IGHM kappa 1-5 3 8 0 CSP+CD27+CD38+T2_072 clr14 III 3-33 4-23 3 18 4 IGHM kappa 1-5 4 8 1 CSP+CD27+CD38+T2_072 clr14 III 3-33 4-23 3 18 3 IGHM kappa 1-5 4 8 1 CSP+CD27+CD38+T2_072 clr14 III 3-33 4-23 3 18 0 IGHM kappa 1-5 4 8 0 CSP+CD27+CD38-T2_072 clr14 III 3-33 4-23 3 18 4 IGHM kappa 1-5 4 8 1 CSP+CD27+CD38+T2_072 clr15 II 3-33 2-15 4 17 2 IGHG1 kappa 1-5 1 8 0 CSP+CD27+CD38-T2_072 clr15 III 3-33 2-15 4 17 0 IGHM kappa 1-5 1 8 0 CSP+CD27+CD38-T2_072 clr16 II 3-33 3-22 4 17 0 IGHG1 kappa 1-5 1 8 0 CSP-CD27+CD38+T2_072 clr16 III 3-33 3-22 4 17 1 IGHG1 kappa 1-5 1 8 1 CSP+CD27+CD38-T2_072 clr16 III 3-33 3-22 4 17 3 IGHM kappa 1-5 1 8 0 CSP+CD27+CD38-T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 kappa 1-5 2 8 1 CSP-CD27+CD38+T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 kappa 1-5 2 8 1 CSP-CD27+CD38+T2_072 clr17 III 3-33 2-15 4 16 4 IGHG1 kappa 1-5 2 8 1 CSP-CD27+CD38+T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 kappa 1-5 2 8 2 CSP+CD27+CD38+T2_072 clr17 III 3-33 2-15 4 16 4 IGHG1 kappa 1-5 2 8 1 CSP+CD27+CD38-T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 kappa 1-5 2 8 1 CSP-CD27+CD38+T2_072 clr17 III 3-33 2-15 4 16 5 IGHG1 kappa 1-5 2 8 2 CSP+CD27+CD38-T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 kappa 1-5 2 8 1 CSP-CD27+CD38+T2_072 clr25 III 4-31 ND 4 15 5 IGHM kappa 4-1 1 9 2 CSP+CD27+CD38-T2_072 clr25 III 4-31 ND 4 15 8 IGHM kappa 4-1 1 9 3 CSP+CD27+CD38-T2_072 clr28 III 4-39 3-10 5 20 18 IGHA1 lambda 9-49 2 11 10 CSP+CD27+CD38+T2_072 clr28 III 4-39 ND 5 20 22 IGHA1 lambda 9-49 2 11 15 CSP+CD27+CD38+T2_072 clr28 III 4-39 3-10 5 20 18 IGHA1 lambda 9-49 2 11 10 CSP+CD27+CD38+T2_072 clr32 II 4-59 3-16 3 14 1 IGHM kappa 2-28 2 8 1 CSP+CD27+CD38-T2_072 clr32 II 4-59 3-16 3 14 0 IGHM kappa 2-28 2 8 0 CSP+CD27+CD38-

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_072 clr32 III 4-59 3-16 3 14 3 IGHM kappa 2-28 2 8 0 CSP+CD27+CD38-T2_072 clr32 III 4-59 3-16 3 14 2 IGHM kappa 2-28 2 8 1 CSP+CD27+CD38-T2_072 clr32 III 4-59 3-16 3 14 0 IGHM kappa 2-28 2 8 0 CSP+CD27+CD38-T2_072 clr32 III 4-59 3-16 3 14 1 IGHM kappa 2-28 2 8 0 CSP+CD27+CD38+T2_072 clr33 I 4-61 3-10 4 11 23 IGHA2 kappa 3-11 2 9 10 CSP+CD27+CD38-T2_072 clr33 II 4-61 3-10 4 11 40 IGHA2 kappa 3-11 2 9 21 CSP-CD27+CD38+T2_072 clr36 III 3-33 4-17 3 15 3 IGHG1 kappa 1-17 2 9 2 CSP+CD27+CD38+T2_072 clr36 III 3-33 4-17 3 15 3 IGHG1 kappa 1-17 2 9 1 CSP+CD27+CD38-T2_072 clr40 III 3-30-3 5-24 6 21 0 IGHM lambda 2-11 1 10 0 CSP+CD27+CD38-T2_072 clr40 III 3-30-3 5-24 6 22 2 IGHM lambda 2-11 1 10 0 CSP+CD27+CD38-T2_072 clr40 III 3-30-3 5-24 6 22 2 IGHM lambda 2-11 1 10 0 CSP+CD27+CD38-T2_072 clr41 III 3-33 4-17 4 14 13 IGHM kappa 2-24 4 9 4 CSP+CD27+CD38-T2_072 clr41 C 3-33 4-17 4 14 14 IGHM kappa 2-24 4 9 4 CSP+CD27+CD38-T2_072 clr42 III 3-33 3-22 5 17 6 IGHG1 kappa 1-5 1 8 1 CSP+CD27+CD38-T2_072 clr42 III 3-33 3-22 5 17 6 IGHG1 kappa 1-5 1 8 1 CSP-CD27+CD38+T2_073 clr01 II 1-18 4-11 4 15 6 IGHM kappa 3-11 3 8 2 CSP+CD27+CD38-T2_073 clr01 III 1-18 ND 4 15 13 IGHM kappa 3-11 3 8 4 CSP+CD27+CD38-T2_073 clr01 III 1-18 ND 4 15 13 IGHM kappa 3-11 3 8 2 CSP+CD27+CD38-T2_073 clr01 III 1-18 4-11 4 15 18 IGHM kappa 3-11 3 8 2 CSP+CD27+CD38-T2_073 clr01 III 1-18 ND 4 15 18 IGHM kappa 3-11 3 8 5 CSP+CD27+CD38-T2_073 clr04 II 3-23 2-2 4 18 15 IGHM kappa 1-5 1 8 3 CSP+CD27+CD38-T2_073 clr04 II 3-23 2-2 4 18 17 IGHA1 kappa 1-5 1 8 10 CSP+CD27+CD38-T2_073 clr04 II 3-23 2-2 4 18 15 IGHM kappa 1-5 1 8 6 CSP+CD27+CD38-T2_073 clr04 II 3-23 2-2 4 18 17 IGHM kappa 1-5 1 8 3 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 16 IGHM kappa 1-5 1 8 3 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 18 IGHM kappa 1-5 1 8 6 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 13 IGHM kappa 1-5 1 8 6 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 20 IGHM kappa 1-5 1 8 5 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 21 IGHM kappa 1-5 1 8 8 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 15 IGHM kappa 1-5 1 8 4 CSP+CD27+CD38-T2_073 clr04 III 3-23 2-2 4 18 16 IGHM kappa 1-5 1 8 2 CSP+CD27+CD38+T2_073 clr05 II 3-23 4-11 4 9 2 IGHM kappa 1-5 5 9 2 CSP+CD27+CD38-T2_073 clr05 II 3-23 ND 4 9 7 IGHM kappa 1-5 5 9 5 CSP+CD27+CD38+T2_073 clr05 II 3-23 4-11 4 9 13 IGHM kappa 1-5 5 9 10 CSP+CD27+CD38-T2_073 clr05 II 3-23 4-11 4 9 12 IGHM kappa 1-5 5 9 11 CSP+CD27+CD38-T2_073 clr05 II 3-23 4-11 4 9 7 IGHM kappa 1-5 5 9 9 CSP+CD27+CD38-T2_073 clr05 II 3-23 ND 4 9 9 IGHM kappa 1-5 5 9 8 CSP+CD27+CD38-T2_073 clr05 II 3-23 4-11 4 9 12 IGHM kappa 1-5 5 9 11 CSP+CD27+CD38-T2_073 clr05 II 3-23 ND 4 9 11 IGHM kappa 1-5 5 9 9 CSP+CD27+CD38+T2_073 clr05 II 3-23 ND 4 9 9 IGHM kappa 1-5 5 9 8 CSP+CD27+CD38-T2_073 clr05 II 3-23 4-11 4 9 23 IGHM kappa 1-5 5 9 13 CSP+CD27+CD38+T2_073 clr05 II 3-23 4-11 4 9 16 IGHM kappa 1-5 5 9 17 CSP+CD27+CD38+T2_073 clr05 II 3-23 4-11 4 9 7 IGHM kappa 1-5 5 9 8 CSP+CD27+CD38+T2_073 clr05 II 3-23 ND 4 9 7 IGHM kappa 1-5 5 9 1 CSP+CD27+CD38+T2_073 clr05 II 3-23 4-11 4 9 6 IGHM kappa 1-5 5 9 8 CSP+CD27+CD38-T2_073 clr05 III 3-23 ND 4 9 13 IGHM kappa 1-5 5 9 13 CSP+CD27+CD38-T2_073 clr05 III 3-23 ND 4 9 5 IGHM kappa 1-5 5 9 5 CSP+CD27+CD38+T2_073 clr05 III 3-23 ND 4 9 5 IGHM kappa 1-5 5 9 5 CSP+CD27+CD38-T2_073 clr05 III 3-23 ND 4 9 5 IGHM kappa 1-5 5 9 5 CSP+CD27+CD38+T2_073 clr05 III 3-23 ND 4 9 8 IGHM kappa 1-5 5 9 8 CSP+CD27+CD38-T2_073 clr05 III 3-23 4-11 4 9 18 IGHM kappa 1-5 5 9 14 CSP+CD27+CD38-T2_073 clr06 II 3-23 2-2 6 18 3 IGHM kappa 1-5 4 8 4 CSP+CD27+CD38-T2_073 clr06 II 3-23 2-2 6 18 12 IGHM kappa 1-5 1 8 5 CSP+CD27+CD38-T2_073 clr06 II 3-23 2-2 6 18 13 IGHA2 kappa 1-5 4 8 9 CSP+CD27+CD38-T2_073 clr07 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_073 clr07 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_073 clr07 III 3-23 6-13 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_073 clr07 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_073 clr07 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_073 clr07 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_073 clr07 III 3-23 6-19 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38+T2_073 clr08 II 3-30 6-19 4 12 9 IGHM lambda 2-8 3 9 6 CSP+CD27+CD38-T2_073 clr08 III 3-30 6-19 4 12 6 IGHM lambda 2-8 3 9 1 CSP-CD27+CD38-T2_073 clr08 III 3-30 6-19 4 12 9 IGHA1 lambda 2-8 3 9 5 CSP+CD27+CD38-T2_073 clr09 III 3-33 3-22 3 16 3 IGHM kappa 1-5 1 8 4 CSP+CD27+CD38-T2_073 clr09 III 3-33 3-22 3 16 0 IGHG3 kappa 1-5 1 8 0 CSP+CD27+CD38-T2_073 clr10 III 3-33 3-22 6 18 13 IGHG1 kappa 1-5 1 8 3 CSP-CD27+CD38+T2_073 clr10 III 3-33 3-22 6 18 12 IGHM kappa 1-5 1 8 3 CSP+CD27+CD38-T2_073 clr11 II 3-33 2-15 4 11 6 IGHM kappa 2-24 2 8 4 CSP+CD27+CD38-T2_073 clr11 III 3-33 2-15 4 11 6 IGHM kappa 2-24 2 8 4 CSP+CD27+CD38-T2_073 clr11 III 3-33 2-15 4 11 6 IGHM kappa 2-24 2 8 4 CSP+CD27+CD38-T2_073 clr12 II 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr12 II 3-33 3-9 6 12 9 IGHM kappa 2-30 2 10 1 CSP+CD27+CD38-T2_073 clr12 II 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr12 II 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP-CD27+CD38+T2_073 clr12 II 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38+T2_073 clr12 II 3-33 3-9 6 12 11 IGHM kappa 2-30 2 10 1 CSP+CD27+CD38-T2_073 clr12 II 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr12 II 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38+T2_073 clr12 III 3-33 ND 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr12 III 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr12 III 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr12 III 3-33 3-9 6 12 7 IGHM kappa 2-30 2 10 6 CSP+CD27+CD38-T2_073 clr13 III 3-33 3-22 4 19 1 IGHM kappa 3-11 4 9 0 CSP+CD27+CD38-T2_073 clr13 III 3-33 3-22 4 19 2 IGHM kappa 3-11 4 9 3 CSP+CD27+CD38-T2_073 clr14 III 3-48 3-10 4 11 9 IGHA1 kappa 2D-29 4 9 8 CSP+CD27+CD38-T2_073 clr14 III 3-48 3-10 4 11 9 IGHA1 kappa 2D-29 4 9 8 CSP+CD27+CD38-T2_073 clr15 II 3-49 3-16 4 13 0 IGHM kappa 2D-29 1 9 0 CSP+CD27+CD38+T2_073 clr15 III 3-49 3-16 4 13 2 IGHG3 kappa 2D-29 1 9 2 CSP-CD27+CD38+T2_073 clr15 III 3-49 3-16 4 13 2 IGHM kappa 2D-29 1 9 2 CSP+CD27+CD38-T2_073 clr16 III 3-49 6-19 4 14 1 IGHM kappa 4-1 2 9 0 CSP+CD27+CD38-T2_073 clr16 III 3-49 6-19 4 14 1 IGHM kappa 4-1 2 9 0 CSP+CD27+CD38-T2_073 clr16 III 3-49 6-19 4 14 0 IGHM kappa 4-1 2 9 0 CSP+CD27+CD38-T2_073 clr16 III 3-49 6-19 4 14 2 IGHG1 kappa 4-1 2 9 5 CSP-CD27+CD38+T2_073 clr16 III 3-49 6-19 4 14 0 IGHG1 kappa 4-1 2 9 0 CSP+CD27+CD38-T2_073 clr16 III 3-49 6-19 4 14 1 IGHM kappa 4-1 2 9 0 CSP+CD27+CD38+T2_073 clr17 II 3-49 2-15 6 13 0 IGHM kappa 2D-29 2 9 0 CSP+CD27+CD38+T2_073 clr17 II 3-49 2-15 6 13 0 IGHM kappa 2D-29 2 9 0 CSP+CD27+CD38+T2_073 clr17 II 3-49 2-15 6 13 0 IGHM kappa 2D-29 2 9 0 CSP+CD27+CD38-T2_073 clr17 III 3-49 2-15 6 13 3 IGHM kappa 2D-29 2 9 3 CSP+CD27+CD38-T2_073 clr18 III 3-49 3-10 4 13 0 IGHM kappa 1-5 1 8 0 CSP+CD27+CD38-T2_073 clr18 III 3-49 3-10 4 13 0 IGHM kappa 1-5 1 8 0 CSP+CD27+CD38-T2_073 clr21 III 3-7 3-10 4 9 1 IGHM kappa 4-1 4 9 0 CSP+CD27+CD38-T2_073 clr21 III 3-7 3-10 4 9 2 IGHM kappa 4-1 4 9 2 CSP+CD27+CD38+T2_073 clr21 III 3-7 3-10 4 9 1 IGHM kappa 4-1 4 9 2 CSP+CD27+CD38-T2_073 clr21 III 3-7 3-10 4 9 2 IGHM kappa 4-1 4 9 0 CSP+CD27+CD38-T2_073 clr21 III 3-7 3-10 4 9 5 IGHM kappa 4-1 4 9 0 CSP+CD27+CD38-T2_073 clr22 III 3-7 3-16 4 16 6 IGHM lambda 4-69 3 9 1 CSP+CD27+CD38-T2_073 clr22 III 3-7 3-16 4 16 6 IGHM lambda 4-69 3 9 1 CSP+CD27+CD38-T2_073 clr22 III 3-7 3-16 4 16 6 IGHM lambda 4-69 3 9 1 CSP+CD27+CD38-

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • table S3. Clonally expanded PfCSP-reactive memory B cell clusters.do

    nor

    clus

    ter i

    d

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    IGHC

    light

    phen

    otyp

    e

    T2_073 clr22 III 3-7 3-16 4 16 9 IGHG1 lambda 4-69 3 9 1 CSP+CD27+CD38-T2_073 clr22 III 3-7 3-16 4 16 6 IGHM lambda 4-69 3 9 1 CSP+CD27+CD38+T2_073 clr22 III 3-7 3-16 4 16 6 IGHM lambda 4-69 3 9 1 CSP+CD27+CD38-T2_073 clr24 III 3-74 3-10 4 16 0 IGHM lambda 9-49 2 9 0 CSP+CD27+CD38-T2_073 clr24 III 3-74 3-10 4 16 0 IGHM lambda 9-49 2 9 0 CSP+CD27+CD38-T2_073 clr28 III 3-23 4-11 4 14 0 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_073 clr28 III 3-23 4-11 4 14 1 IGHM lambda 1-47 2 11 0 CSP+CD27+CD38-T2_073 clr29 III 3-30-3 3-22 4 21 7 IGHM kappa 3-15 1 9 3 CSP+CD27+CD38-T2_073 clr29 III 3-30-3 3-22 4 21 7 IGHM kappa 3-15 1 9 3 CSP+CD27+CD38-T2_073 clr30 II 3-33 3/OR15-3a 4 11 6 IGHM kappa 2-24 2 8 2 CSP+CD27+CD38-T2_073 clr30 III 3-33 3/OR15-3a 4 11 8 IGHM kappa 2-24 2 8 4 CSP+CD27+CD38-T2_073 clr31 II 3-23 2-2 4 14 16 IGHM lambda 2-5 3 10 9 CSP-CD27+CD38-T2_073 clr31 III 3-23 2-2 4 14 11 IGHM lambda 2-5 3 10 6 CSP+CD27+CD38-T2_073 clr34 II 3-74 6-19 1 7 2 IGHM kappa 2-28 4 8 0 CSP+CD27+CD38-T2_073 clr34 III 3-74 6-19 1 7 8 IGHM kappa 2-28 4 8 0 CSP+CD27+CD38-

    Pf exposure I, II, III, C correspond to first, second, third and challenge exposures respectivelyclr: clusterND: Not determinedCDR3 lengths are in amino acidsSHMs are counted in nucleotide base pairs

    HC

    DR

    3Le

    ngth

    (aa)

    IGHV

    SHM

    (bp)

    IGKV/

    IGLV

    IGKJ/

    IGLJ

    Ligh

    t CD

    R3

    leng

    th(a

    a)

    IGKV/IGLV

    SHM

    (bp)

  • Table S4. Simulation Parameters, Binding Model, GC Simulation Dynamics

    Infection schedule, antigen and limiting factor presence symbol default

    value meaning source / reason

    tvacc [0, 28, 56] Vaccination schedule in days CHMI trial underlying this work (9)

    τdecay 2 days Time constant of exponential Ag decay/removal in the system

    (59)

    pbase 0.005 Base activation probability per free B cell and timestep

    choice leading to 10% activation

    tGC,max day 7 Day until which the GC stays at maximum size onset of Pf blood stage (37)

    τGC decay 10 days, varies

    Time constant of exponential limiting factor decay after tGC,max

    set to reduce GC size faster than normal (58; 60) due to blood stage antigens (60)

    GC dynamics symbol default

    value meaning source / reason

    tinit 3 days Time needed by B cells to become fully activated and migrate to the follicle to form a GC after initial antigenic contact

    (61)

    tAID 3 days Time needed for cells having newly joined the GC before they start acquiring mutations during divisions

    (31)

    thelp 2 hours Time that selected B cells receive survival signals before deciding to divide or differentiate

    order of (30)[several contacts of 10-60 min]

    ndiv 2 number of divisions B cells undergo following selection

    mean in (62)

    tdiv 8 hours Time needed for cell division in the GC after having received survival signal

    (63)

    tdiff 8 hours Time needed for differentiation into a memory cell after having received survival signal

    chosen to match tdiv

    tlife, GC 8 hours Maximum survival time of GC cells in the waiting area

    choice with minor effect on results

    tlife, naive 14 days Lifetime of naïve cells that have not been activated; new naïve cells are continuously introduced into the simulation to keep up the poolsize nnaive

    (64)

    r 0.9 Fraction of cells choosing to divide and recycle instead of leaving as a differentiated cell after receiving survival signal

    (65)

    pPC 0.5 Fraction of exported cells that are of plasma cell phenotype, 1-pPC are exported as memory; plasma cells are not modeled explicitly, thus cells in question are removed from the system

    (66)

  • Binding model & mutations symbol default

    value meaning source / reason

    nkey [1 … 15] Number of residues jointly determining affinity towards a given epitope sequence

    text

    nV 220 Combined length of the VH and VL segments bthr 0.6 Binding threshold in normalized energy units text Kdthr 10-5 M Corresponding binding threshold as dissociation

    constant (28; 67)

    btop 1 Maximum binding strength in normalized energy units

    text

    Kdtop 10-9 M Corresponding maximum binding strength as dissociation constant

    (28; 67)

    perr 0.003 Error probability per codon and division (29; 31) pdeath 0.5 Probability that a replacement mutation in a

    residue relevant for stability leads to a non-functional Ab (and hence cell death)

    (31)

    pblock 0.55 Probability that a mutation in a non-key residue results in blocking of affinity maturation

    mean of values given in (31)

    Simulation size symbol default

    value meaning source / reason

    nGC 50, varies Number of individual GCs in the system text, weak affect on results

    nLF 25, varies Number of limiting factors (TFH cells) per GC leads to GCs of 500 cells in steady state, in range of (68)

    nnaive 1000, varies Steady state number of potentially binding free naïve cells per GC

    nfreemem 100 Number of binding free memory cells from former infections per GC at t=0

    tstep 2 hours Simulation timestep chosen to match smallest simulated time unit (thelp)

  • Binding model

    The binding model assumes that two levels of complementarity between antibody

    and epitope contribute to binding. Most amino acids (aa) in the antibody sequence are

    involved in determining the general binding site shape and therefore whether binding is

    possible or not. Biologically, this may roughly but not exclusively correspond to the V and

    J segment encoded framework regions. As we are treating only one antigen at a time,

    this is initially assumed for all B cells participating in the simulation (though it may be

    destroyed by mutations as described below). Their binding behavior differs due to the

    second level of binding, which is determined by an explicitly modeled sequence of aa

    residues. For an antigenic determinant of length nkey aa, an equal number of key aa

    positions are considered strongly relevant for binding. This number may be very low for

    haptens, where one antibody key mutation can strongly increase affinity, but is higher for

    larger and more complex epitopes. The efficiency of selection for beneficial mutations in

    GCs depends on the improvement conveyed by each individual mutation as previously

    modeled (55). To compare B cell immune responses to antigens of different complexities

    we therefore allowed varying numbers of nkey residues to determine the binding strength.

    Using the full physiological aa alphabet we modeled the combined IgH and IgL

    variable region length of 220 aa, nkey of which were explicitly modeled by a sequence of

    randomly chosen codons. An antigenic epitope of complexity nkey was similarly modeled

    by nkey random codons. For each of the nkey resulting pairs of residues in epitope and

    antibody key positions, respectively, an energy-like quantity was taken from the Thomas-

    Dill contact matrix for 20 aa and contributions were summed up (56). As the lowest and

    highest possible binding energies are known in this model, these values were used to

    rescale all binding energies into normalized energy values Ebind between 0 (worst binder)

    and 1 (best binder). With an increasing number of nkey residues, good binders become

    increasingly rare as the peak at intermediate binding energies becomes sharper. This

    generic consequence of the law of large numbers needs to be taken into account when

    comparing antigenic challenges of different nkey (see section GC Dynamics). To introduce

  • higher degeneracy at the low quality end of the spectrum, the lower affinity threshold of

    Kd = 10-5 M was fixed to Ebind = 0.6. The best binders, Ebind = 1, were set to Kd = 10-9 M.

    Consequently, in agreement with experimental findings (57), most energy-affecting

    mutations in binding antibodies have negative effects.

    During division, single base pair mutations occur with probability perr = 3*10-3

    (assuming an error rate of 10-3 per base pair (29), the probabilities for 0 to 3 mutations

    within a single codon are p0 = 0.997, p1 = 3*10-3, p2,3 < 10-5 – double and triple mutations

    were therefore ignored). The number of binding site mutations is drawn from a binomial

    distribution with n = nkey and p = perr. The same applies for the scaffold region with n =

    220-nkey and p = perr. For nkey = 10 this results in mean values of 0.63 mutations in the

    scaffold region (first level of binding) and 0.03 mutations in the key positions determining

    the quality of binding (second level of binding).

    Mutations in the key aa may change the identity of the specifically modeled

    residue in question. Transition probabilities between aa are calculated taking into

    account all codons coding for both the start and the end aa and using only transitions

    accessible by single base pair exchanges. All base pair exchanges are assumed to be

    equally likely. Using a full aa alphabet with codon-determined transition probabilities and

    an interaction energy matrix based on real protein-protein interactions naturally

    introduces the conservatism of the genetic code (S mutations and R mutations by

    functionally similar aa are more likely than in a random replacement model). The higher

    the affinity of a sequence is, the less likely it becomes to identify beneficial mutations.

    The scaffold region is responsible for general shape correspondence with a given

    epitope and stability of the antibody. Mutations to this area, which is not modeled as an

    explicit sequence for computational efficiency, can lead to three different outcomes. On

    average, 25% of mutations are silent and are not considered further. For R mutations

    resulting in unfoldable antibodies or loss of antigen-binding, pdeath lead to B cell death.

    For non-lethal aa exchanges, pblock is considering blocking mutations in antibodies that

    cannot bind the target with higher affinity than their germline ancestor even if beneficial

  • key region mutations are present (31). This is a simplified way of introducing epistasis

    into the model.

    GC Dynamics

    At first, the simulation generates an epitope sequence of length nkey. Next, a

    reservoir list of antibody key sequences is engineered such that the distribution of

    binding energies between sequences in the reservoir and the epitope sequence conform

    to a discretized Gaussian distribution with mean Ebind = 0.5 and standard deviation 0.1 for

    values above the activation threshold Ebind = 0.6, mimicking the distribution naturally

    arising for randomly drawn sequences for nkey = 10. Here, we introduced the possibility of

    enforcing a binding energy distribution to allow comparison of GC efficiencies across

    challenges of different complexities without artifacts introduced by different quality

    unselected repertoires.

    Naïve and unspecific memory B cells are equipped with randomly picked

    sequences from the pre-generated reservoir throughout the simulation. Memory cells are

    immortal on the simulated timescale of 100 days whereas naïve cells die after 𝑡!"#$,!"ï!"

    unless activated. To maintain a constant pool size, naïve cells are added to the system

    with rate 𝑟!"#$% = 𝑛!"#$%/𝑡!"#$,!"#$%, leading to a continuous turnover of the naïve cells.

    When antigen is added at 𝑡!"##,!, its concentration decays exponentially from a

    starting value determined by the assumed vaccination dose with 𝜏!"#$%, giving the time

    curve 𝐴𝑔 𝑡 − 𝑡!"##,! = 𝑒!(!!!!"##,!)/!!"#$% for 𝑡 > 𝑡!"##,! per antigen exposure. Similarly, the

    number of TFH cells at a follicular site (determining the size of the GC forming there) is at

    its maximum value nLF between the time needed for both B and TFH cells to migrate

    there, 𝑡!"!# , and 𝑡!",!"# , whereafter their number decreases exponentially with decay

    constant 𝜏 !" !"#$%. This roughly mimics experimentally observed GC growth and decline

    (58). While antigen is present in the system, every free B cell (naïve and memory) gets

    activated and primed to join a GC with probability proportional to the antigen

  • concentration at each time step. This activation step is independent of affinity and

    competition for antigen.

    Once arrived at the follicular site, activated cells enter the GC where they

    compete for TFH signals to either divide and recycle or exit as differentiated effector cells.

    Competition is based on each cell’s antigen affinity and the number of currently available

    TFH cells. Winners are drawn based on a Boltzmann distribution at every time step: the

    probability pi for a cell with binding energy Ei to be selected in a pool of J cells is

    𝑝! =!!!!!/!!

    !!!!!/!!!! . Cells that divide and recycle or differentiate and exit after having received

    survival signals are chosen randomly. Differentiating cells turn into memory B cells and

    long-lived plasma cells with equal probabilities. Plasma cells are not modeled and

    therefore disappear from the simulation whereas memory B cells rejoin the pool for

    activation and priming to reenter GCs during future immune responses.

    Experimental observations show that mutations in GCs start only after a period of

    mutation-free expansion (31). Therefore, divisions happening in the time frame of tAID

    days after a B cell clone entered the GC are exempt from the mutational procedure

    described above.

    The following page contains the simulation algorithm as simplified pseudocode.

    The source code of the vaccination simulation is publicly available at

    https://github.com/LiBuchauer/gc_memo (doi:10.5281/zenodo.1048052).

  • 1: function Germinal Center Model

    2: Set tnow = 0.

    3: Create an antigenic determinant sequence of length nkey.4: Create a large (see text) list Lseq of antibody sequences of length nkey so that the distribution of binding

    energies between these sequences and the antigen sequence is as requested (see text).

    5: Create a list of nnaïve · nGC naïve B cells with sequences drawn from Lseq and mutation count mV = 0.6: Create a list of nfreemem · nGC unspecific B cells with sequences drawn from Lseq and

    mV = UniformDistribution[0, 40].7: Create a list of nGC empty waiting lists.

    8: Calculate the time curve Ag(t) of antigenic presence in the system (see text).9: Calculate the time curve LF (t) of limiting factor presence in the follicular sites (see text).

    10: Open an empty event list for each GC to store events that are executed with a time delay.

    11: while tnow < tmax do

    12: Remove inactive naïve cells that are older than tlife, naïve.13: if number of free naïve cells < nnaïve · nGC then14: Create naïve B cells with rate nnaïve · nGC/tlife, naïve.

    15: In each GC, remove waiting B cells that have been there for longer than tlife, GC.

    % Events consist of (event type, execution time, GC ID, list of cells concerned by the event).

    16: if event list contains events with texecution = tnow then17: for every one of these events do

    18: if event is of type ‘Enter’ then

    19: Distribute the cells randomly to the GC waiting lists.

    20: else if event is of type ‘Divide’ then

    21: Make two possibly mutated daughter cells from every mother (see text).

    22: Append the viable daughter cells to the GC’s waiting list.

    23: else if event is of type ‘Differentiate’ then

    24: Append the cells to the free memory list.

    25: Discard event.

    26: if antigen is present in the system at tnow then27: Create empty list Lact for newly activated cells.28: for every cell in the free naïve and memory pools do

    29: Activate with probability Ag(tnow) · pbase.30: if activation is successful then append cell to Lact31: Create event of type ‘Enter’ with texecution = tnow + tinit and Lact.32: Append event to event list.

    33: if limiting factors are present in the follicles at tnow then34: for every GC do

    35: if there are B cells waiting for survival signals then

    36: Choose LF (tnow) waiting cells for survival according to Boltzmann-distributed selectionprobabilities (see text).

    37: In order to incorporate double division after selection, directly make two possibly mutated

    daughter sequences from every mother (see text).

    38: Create event of type ‘Divide’ with texecution = tnow + 2tdiv and a randomly selected fractionprecycle of the viable daughters from the first division round.

    39: Create event of type ‘Differentiate’ with texecution = tnow + tdiv + tdiff and the remainingchosen cells.

    40: Append events to the event list.

    41: Set tnow = tnow + tstep.

  • table S5. PfCSP reactive memory B cell antibodies with 8-amino acid-long KCDR3.do

    nor

    Clu

    ster

    id

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    HSH

    M (b

    p)

    IGHC

    IGKV

    IGKJ

    KSH

    M (b

    p)

    T2_017 non-cluster I 4-59 3-22 3 10 0 IGHM 3-20 3 0T2_017 non-cluster I 1-18 3-3 6 19 5 IGHA1 3-20 5 3T2_017 non-cluster II 4-31 NA 4 7 0 IGHM 3-20 5 0

    T2_026 non-cluster I 3-66 6-19 4 15 6 IGHM 1-5 1 3T2_026 non-cluster III 4-4 1-26 6 22 15 IGHM 2-28 1 5T2_026 non-cluster III 1-3 3-22 4 15 0 IGHM 2-28 3 0T2_026 non-cluster C 3-33 6-19 4 12 3 IGHM 2-24 2 0T2_026 non-cluster C 1-2 5-12 6 20 7 IGHM 2-28 1 2T2_026 non-cluster C 4-59 5-24 4 14 11 IGHM 3-15 2 11T2_026 non-cluster C 3-49 3-16 6 22 3 IGHG1 2-26 4 0T2_026 non-cluster C 1-3 5-12 5 12 14 IGHG2 3-20 3 12T2_026 non-cluster C 5-51 3-3 4 10 4 IGHM 3-11 4 5T2_026 non-cluster C 3-33 4-17 4 11 6 IGHG1 2-28 1 2T2_026 non-cluster C 1-3 3-10 5 15 0 IGHM 1-5 1 1T2_026 non-cluster C 3-33 3-10 4 18 5 IGHM 1-33 4 8

    T2_035 non-cluster I 3-7 3-16 4 12 18 IGHM 4-1 4 12T2_035 non-cluster I 3-33 6-19 4 10 6 IGHM 2-24 1 0 6.78E-06 59.3T2_035 non-cluster I 3-30 6-19 6 21 0 IGHM 1-39 1 0T2_035 non-cluster II 4-59 5-18 3 17 0 IGHM 1-5 1 0T2_035 non-cluster III 3-30 6-13 4 14 0 IGHM 3-11 4 0T2_035 non-cluster III 3-33 3-22 4 15 0 IGHM 3-20 2 0 1.59E-05 33.5T2_035 non-cluster III 3-33 4-17 4 14 0 IGHM 1-5 1 0 1.18E-05 54.6T2_035 non-cluster C 3-30 3-22 4 15 9 IGHM 3-11 2 6

    T2_042 clr16 III 3-33 6-19 4 12 0 IGHM 2-24 1 0T2_042 clr16 C 3-33 6-19 4 12 2 IGHM 2-24 1 0

    T2_042 non-cluster III 3-33 6-6 5 14 1 IGHG1 1-39 1 1T2_042 non-cluster III 3-53 1-1 4 11 4 IGHM 1-5 1 9T2_042 non-cluster C 3-53 3-3 4 16 18 IGHM 3-15 1 13T2_042 non-cluster C 4-59 6-13 4 13 8 IGHM 1-5 1 11T2_042 non-cluster C 3-33 6-19 4 16 0 IGHM 1-5 4 1 6.36E-07 73.2T2_042 non-cluster C 3-33 3-16 3 17 3 IGHM 1-5 1 3 5.64E-08 94.3T2_042 non-cluster C 3-7 2/OR15-2a 4 6 26 IGHM 1-33 5 13

    T2_051 non-cluster III 4-59 2-15 3 14 0 IGHM 2-28 2 0T2_051 non-cluster III 4-39 3-22 4 12 0 IGHM 3-20 4 0T2_051 non-cluster III 4-38-2 5-12 4 11 2 IGHM 3-20 3 0

    T2_071 clr02 II 1-2 2-15 4 13 6 IGHM 2-28 2 5T2_071 clr02 II 1-2 2-15 4 13 6 IGHM 2-28 2 5

    HC

    DR

    3Le

    ngth

    (aa)

    Kd (

    M)

    Mea

    sure

    men

    t1

    Kd (

    M)

    Mea

    sure

    men

    t2

    Pf s

    pzin

    hibi

    tion

    (%)

  • table S5. PfCSP reactive memory B cell antibodies with 8-amino acid-long KCDR3.do

    nor

    Clu

    ster

    id

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    HSH

    M (b

    p)

    IGHC

    IGKV

    IGKJ

    KSH

    M (b

    p)

    T2_071 clr02 II 1-2 2-15 4 13 6 IGHG1 2-28 2 5 1.20E-05 7.13E-06 86.6T2_071 clr02 III 1-2 2-15 4 13 6 IGHM 2-28 2 5T2_071 clr02 III 1-2 2-15 4 13 6 IGHM 2-28 2 5T2_071 clr02 III 1-2 2-15 4 13 6 IGHM 2-28 2 5

    T2_071 clr16 III 3-23 6-13 3 15 13 IGHM 3-20 1 4 ND ND 46.2T2_071 clr16 C 3-23 6-13 3 15 13 IGHM 3-20 1 4T2_071 clr16 C 3-23 6-13 3 15 13 IGHM 3-20 1 4T2_071 clr16 C 3-23 6-13 3 15 13 IGHM 3-20 1 4T2_071 clr16 C 3-23 6-13 3 15 13 IGHM 3-20 1 4T2_071 clr16 C 3-23 6-13 3 15 15 IGHM 3-20 1 5 ND ND 36.5T2_071 clr16 C 3-23 6-13 3 15 13 IGHM 3-20 1 4 ND ND 13.4T2_071 clr16 C 3-23 6-13 3 15 14 IGHM 3-20 1 5 ND ND 41.6

    T2_071 clr27 III 3-33 2-15 4 17 0 IGHG1 1-5 1 2 3.13E-08 9.01E-09 96.5T2_071 clr27 C 3-33 2-15 4 17 0 IGHG1 1-5 1 2 3.07E-08 1.04E-08 100

    T2_071 clr29 III 3-33 5-24 6 10 5 IGHG1 2-24 2 2 1.68E-05 1.52E-06 57.8T2_071 clr29 C 3-33 5-24 6 10 5 IGHM 2-24 2 2

    T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3T2_071 clr30 III 3-33 1-7 4 12 9 IGHM 2-24 2 3

    T2_071 clr31 III 3-33 1-1 5 11 2 IGHM 3-11 2 2T2_071 clr31 III 3-33 1-1 5 11 2 IGHM 3-11 2 3 1.94E-06 4.54E-07 79.7T2_071 clr31 III 3-33 1-1 5 11 2 IGHM 3-11 2 2 3.90E-06 4.76E-07 74.8

    HC

    DR

    3Le

    ngth

    (aa)

    Kd (

    M)

    Mea

    sure

    men

    t1

    Kd (

    M)

    Mea

    sure

    men

    t2

    Pf s

    pzin

    hibi

    tion

    (%)

  • table S5. PfCSP reactive memory B cell antibodies with 8-amino acid-long KCDR3.do

    nor

    Clu

    ster

    id

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    HSH

    M (b

    p)

    IGHC

    IGKV

    IGKJ

    KSH

    M (b

    p)

    T2_071 clr33 II 3-33 4-11 6 13 14 IGHM 3-20 2 5T2_071 clr33 II 3-33 4-11 6 13 5 IGHM 3-20 2 1 2.70E-07 3.40E-07 74T2_071 clr33 II 3-33 4-11 6 13 5 IGHM 3-20 2 1 2.85E-07 3.95E-07 72.5T2_071 clr33 II 3-33 4-11 6 13 8 IGHM 3-20 2 1 2.44E-07 2.59E-07 71.9T2_071 clr33 II 3-33 4-11 6 13 14 IGHM 3-20 2 5 2.81E-07 2.26E-07 83.5T2_071 clr33 II 3-33 4-11 6 13 8 IGHM 3-20 2 3 2.23E-07 3.01E-07 85.4T2_071 clr33 III 3-33 4-11 6 13 9 IGHM 3-20 2 2T2_071 clr33 III 3-33 4-11 6 13 10 IGHM 3-20 2 3T2_071 clr33 III 3-33 4-11 6 13 7 IGHM 3-20 2 5 5.20E-08 4.82E-08 100T2_071 clr33 III 3-33 4-11 6 13 7 IGHM 3-20 2 2 5.04E-08 5.77E-08 94.1T2_071 clr33 III 3-33 4-11 6 13 10 IGHM 3-20 2 3 2.60E-09 2.49E-09 100T2_071 clr33 III 3-33 4-11 6 13 7 IGHM 3-20 2 2T2_071 clr33 III 3-33 4-11 6 13 7 IGHM 3-20 2 2T2_071 clr33 III 3-33 4-11 6 13 7 IGHM 3-20 2 2 5.10E-08 5.00E-08 90.5

    T2_071 non-cluster III 4-4 2-15 6 23 2 IGHM 3-20 1 6T2_071 non-cluster III 3-33 1-1 5 11 2 IGHM 3-11 2 2T2_071 non-cluster III 3-33 3-22 4 17 1 IGHM 1-5 1 1 1.33E-07 1.34E-07 97.2T2_071 non-cluster III 3-33 1/OR15-1a 4 11 10 IGHM 2-24 2 1 4.76E-06 8.85E-06 NAT2_071 non-cluster III 1-46 2-2 6 20 0 IGHM 1-5 1 0T2_071 non-cluster III 3-33 6-13 4 15 0 IGHM 3-11 4 0 4.85E-08 4.25E-08 NA

    T2_071 non-cluster C 3-23 5-24 4 15 23 IGHA2 4-1 1 8

    T2_072 clr13 III 3-33 4-17 3 20 0 IGHM 1-5 3 0 2.20E-08 4.37E-08 100T2_072 clr13 III 3-33 4-17 3 20 0 IGHM 1-5 3 0T2_072 clr13 III 3-33 4-17 3 20 3 IGHG1 1-5 3 1 6.32E-09 1.73E-08 86.7T2_072 clr13 III 3-33 4-17 3 20 0 IGHM 1-5 3 0T2_072 clr13 III 3-33 4-17 3 20 0 IGHM 1-5 3 0T2_072 clr13 III 3-33 4-17 3 20 0 IGHM 1-5 3 0 2.18E-08 1.62E-08 89.6T2_072 clr13 III 3-33 4-17 3 20 0 IGHM 1-5 3 0T2_072 clr13 C 3-33 4-17 3 20 0 IGHM 1-5 3 0

    T2_072 clr14 III 3-33 4-23 3 18 4 IGHM 1-5 4 1 52.9T2_072 clr14 III 3-33 4-23 3 18 3 IGHM 1-5 4 1 5.72E-09 4.83E-09 91.5T2_072 clr14 III 3-33 4-23 3 18 0 IGHM 1-5 4 0 1.58E-06 1.53E-06 52.9T2_072 clr14 III 3-33 4-23 3 18 4 IGHM 1-5 4 1

    T2_072 clr15 II 3-33 2-15 4 17 2 IGHG1 1-5 1 0 4.59E-09 1.84E-09 100T2_072 clr15 III 3-33 2-15 4 17 0 IGHM 1-5 1 0 7.04E-09 5.60E-09 100

    HC

    DR

    3Le

    ngth

    (aa)

    Kd (

    M)

    Mea

    sure

    men

    t1

    Kd (

    M)

    Mea

    sure

    men

    t2

    Pf s

    pzin

    hibi

    tion

    (%)

  • table S5. PfCSP reactive memory B cell antibodies with 8-amino acid-long KCDR3.do

    nor

    Clu

    ster

    id

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    HSH

    M (b

    p)

    IGHC

    IGKV

    IGKJ

    KSH

    M (b

    p)

    T2_072 clr16 II 3-33 3-22 4 17 0 IGHG1 1-5 1 0 1.87E-08 9.89E-08 81.7T2_072 clr16 III 3-33 3-22 4 17 1 IGHG1 1-5 1 1 1.75E-08 9.59E-08 80.8T2_072 clr16 III 3-33 3-22 4 17 3 IGHM 1-5 1 0 1.36E-08 7.88E-08 97.5

    T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 1-5 2 1 2.36E-09 2.55E-09 92.2T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 1-5 2 1 4.69E-09 5.29E-09 100T2_072 clr17 III 3-33 2-15 4 16 3 IGHG1 1-5 2 2 3.48E-09 7.85E-09 89.3

    T2_072 clr32 II 4-59 3-16 3 14 1 IGHM 2-28 2 1 9.78E-06 6.19E-07 81.2T2_072 clr32 II 4-59 3-16 3 14 0 IGHM 2-28 2 0 1.00E-05 9.82E-06 76.8T2_072 clr32 III 4-59 3-16 3 14 3 IGHM 2-28 2 0 9.93E-06 9.08E-06 74.7T2_072 clr32 III 4-59 3-16 3 14 2 IGHM 2-28 2 1 9.54E-06 2.23E-06 NAT2_072 clr32 III 4-59 3-16 3 14 0 IGHM 2-28 2 0T2_072 clr32 III 4-59 3-16 3 14 1 IGHM 2-28 2 0

    T2_072 non-cluster I 4-39 2-8 3 11 12 IGHM 3-20 3 7T2_072 non-cluster II 3-33 2-2 3 21 5 IGHM 1-5 1 1 1.94E-07 66.1T2_072 non-cluster II 3-33 6-13 5 16 0 IGHM 3-20 3 0T2_072 non-cluster II 3-33 3-22 4 17 0 IGHM 1-5 1 0T2_072 non-cluster III 3-33 3-22 4 14 2 IGHG1 3-11 3 0T2_072 non-cluster III 3-74 1-1 5 6 0 IGHG1 2-28 4 0T2_072 non-cluster III 3-33 5-24 3 12 4 IGHG1 1-5 1 0 2.63E-08 96.7T2_072 non-cluster III 3-33 3-22 4 14 7 IGHG1 1-5 1 3 1.83E-08 86.4T2_072 non-cluster III 3-74 1-14 5 6 0 IGHM 2-28 4 0 2.38E-06 NAT2_072 non-cluster III 3-33 3-10 4 17 6 IGHM 3-15 2 2T2_072 non-cluster III 3-74 2-15 4 6 0 IGHM 2-28 4 0T2_072 non-cluster III 3-33 2-8 3 20 5 IGHG1 1-5 2 0 6.92E-10 7.57E-10 100T2_072 non-cluster III 3-33 3-10 4 15 1 IGHM 1-5 1 0T2_072 non-cluster III 3-33 3-10 4 14 4 IGHG1 1-33 3 5T2_072 non-cluster III 3-33 4-23 3 17 2 IGHG1 1-5 1 1 6.16E-10 6.44E-10 100T2_072 non-cluster III 3-33 6-19 4 16 5 IGHM 3-15 1 0T2_072 non-cluster III 3-33 2-2 4 17 0 IGHM 1-5 3 0 1.18E-08 100T2_072 non-cluster III 3-33 3-10 4 14 1 IGHM 1-12 1 3T2_072 non-cluster III 3-33 2-15 4 17 1 IGHM 1-5 1 1T2_072 non-cluster III 3-9 6-13 3 15 0 IGHM 1-39 3 11T2_072 non-cluster III 1-69 3-10 3 16 1 IGHM 1-5 1 0T2_072 non-cluster III 3-33 3-3 3 11 2 IGHA1 2-30 2 1T2_072 non-cluster III 3-33 2-15 4 17 0 IGHM 1-5 1 0T2_072 non-cluster III 3-33 3-9 4 21 0 IGHM 3-15 1 1T2_072 non-cluster III 3-33 4-23 3 18 4 IGHM 1-5 4 1T2_072 non-cluster III 1-2 4-23 3 14 0 IGHM 1-5 1 0T2_072 non-cluster III 3-33 3-22 5 17 6 IGHG1 1-5 1 1 1.24E-09 8.96E-10 100

    HC

    DR

    3Le

    ngth

    (aa)

    Kd (

    M)

    Mea

    sure

    men

    t1

    Kd (

    M)

    Mea

    sure

    men

    t2

    Pf s

    pzin

    hibi

    tion

    (%)

  • table S5. PfCSP reactive memory B cell antibodies with 8-amino acid-long KCDR3.do

    nor

    Clu

    ster

    id

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    HSH

    M (b

    p)

    IGHC

    IGKV

    IGKJ

    KSH

    M (b

    p)

    T2_073 clr01 II 1-18 4-11 4 15 6 IGHM 3-11 3 2 9.06E-07 4.67E-07 33.5T2_073 clr01 III 1-18 ND 4 15 13 IGHM 3-11 3 4 5.74E-06 4.24E-06 0T2_073 clr01 III 1-18 ND 4 15 13 IGHM 3-11 3 2 7.04E-06 6.07E-06 12.4T2_073 clr01 III 1-18 4-11 4 15 18 IGHM 3-11 3 2T2_073 clr01 III 1-18 ND 4 15 18 IGHM 3-11 3 5 7.02E-06 7.22E-06 NA

    T2_073 clr04 II 3-23 2-2 4 18 15 IGHM 1-5 1 3 4.47E-06 4.31E-06 59.4T2_073 clr04 II 3-23 2-2 4 18 17 IGHA1 1-5 1 10 2.39E-06 1.32E-06 60.5T2_073 clr04 II 3-23 2-2 4 18 15 IGHM 1-5 1 6 2.18E-06 1.80E-06 77.6T2_073 clr04 II 3-23 2-2 4 18 17 IGHM 1-5 1 3 5.24E-06 6.01E-06 51.7T2_073 clr04 III 3-23 2-2 4 18 16 IGHM 1-5 1 3T2_073 clr04 III 3-23 2-2 4 18 18 IGHM 1-5 1 6 4.01E-06 4.08E-06 59T2_073 clr04 III 3-23 2-2 4 18 13 IGHM 1-5 1 6 2.12E-06 1.91E-06 74.7T2_073 clr04 III 3-23 2-2 4 18 20 IGHM 1-5 1 5 3.54E-06 1.11E-06 69.1T2_073 clr04 III 3-23 2-2 4 18 21 IGHM 1-5 1 8 3.63E-06 1.59E-06 54.9T2_073 clr04 III 3-23 2-2 4 18 15 IGHM 1-5 1 4 3.63E-06 1.03E-06 68.2T2_073 clr04 III 3-23 2-2 4 18 16 IGHM 1-5 1 2 5.26E-06 3.66E-06 58.2

    T2_073 clr06 II 3-23 2-2 6 18 3 IGHM 1-5 4 4 2.21E-06 34.3T2_073 clr06 II 3-23 2-2 6 18 12 IGHM 1-5 1 5 1.03E-06 NAT2_073 clr06 II 3-23 2-2 6 18 13 IGHA2 1-5 4 9

    T2_073 clr09 III 3-33 3-22 3 16 3 IGHM 1-5 1 4 1.14E-08 4.56E-08 100T2_073 clr09 III 3-33 3-22 3 16 0 IGHG3 1-5 1 0

    T2_073 clr11 II 3-33 2-15 4 11 6 IGHM 2-24 2 4T2_073 clr11 III 3-33 2-15 4 11 6 IGHM 2-24 2 4T2_073 clr11 III 3-33 2-15 4 11 6 IGHM 2-24 2 4

    T2_073 clr18 III 3-49 3-10 4 13 0 IGHM 1-5 1 0 3.43E-06 9.42E-07 37.6T2_073 clr18 III 3-49 3-10 4 13 0 IGHM 1-5 1 0 3.51E-06 8.79E-07 41

    T2_073 clr30 II 3-33 3/OR15-3a 4 11 6 IGHM 2-24 2 2T2_073 clr30 III 3-33 3/OR15-3a 4 11 8 IGHM 2-24 2 4

    T2_073 clr34 II 3-74 6-19 1 7 2 IGHM 2-28 4 0T2_073 clr34 III 3-74 6-19 1 7 8 IGHM 2-28 4 0

    T2_073 non-cluster II 3-48 3-10 4 13 0 IGHM 1-5 1 5T2_073 non-cluster II 4-39 3-16 3 19 0 IGHM 1-39 1 0T2_073 non-cluster II 3-23 5-18 4 16 23 IGHG1 3-11 3 11T2_073 non-cluster II 3-33 3-22 3 22 2 IGHM 1-37 1 6

    HC

    DR

    3Le

    ngth

    (aa)

    Kd (

    M)

    Mea

    sure

    men

    t1

    Kd (

    M)

    Mea

    sure

    men

    t2

    Pf s

    pzin

    hibi

    tion

    (%)

  • table S5. PfCSP reactive memory B cell antibodies with 8-amino acid-long KCDR3.do

    nor

    Clu

    ster

    id

    Pf e

    xpos

    ure

    IGHV

    IGHD

    IGHJ

    HSH

    M (b

    p)

    IGHC

    IGKV

    IGKJ

    KSH

    M (b

    p)

    T2_073 non-cluster III 3-33 6-19 4 18 12 IGHM 2-24 2 4T2_073 non-cluster III 3-33 3-22 4 17 0 IGHG3 1-5 1 0T2_073 non-cluster III 3-30 3-22 6 16 8 IGHM 1-12 3 6T2_073 non-cluster III 3-33 3-16 5 11 4 IGHM 3-11 2 1T2_073 non-cluster III 3-33 2-21 4 15 3 IGHG1 1-5 1 1T2_073 non-cluster III 3-33 3-3 5 14 1 IGHG3 2-28 2 1T2_073 non-cluster III 3-33 6-13 4 15 0 IGHG1 1-39 3 0 NA 68.3T2_073 non-cluster III 3-30 2-15 4 14 4 IGHM 3-11 2 0

    T2_073 non-cluster III 3-33 3-9 4 10 10 IGHM 2-24 2 3T2_073 non-cluster III 3-30 2/OR15-2a 6 14 6 IGHM 3-11 4 2T2_073 non-cluster III 3-33 7-27 4 12 6 IGHM 2-24 2 0T2_073 non-cluster III 3-33 3-22 4 16 1 IGHG1 1-5 1 1 1.95E-09 NAT2_073 non-cluster III 3-33 4-17 3 18 2 IGHM 1-5 1 0T2_073 non-cluster III 3-30 3-22 4 15 0 IGHM 2-30 2 0T2_073 non-cluster III 3-33 1-26 4 15 0 IGHM 3-15 2 1T2_073 non-cluster III 3-33 6-13 4 17 3 IGHM 1-5 3 2T2_073 non-cluster III 3-33 6-13 3 16 1 IGHM 1-5 1 1T2_073 non-cluster III 3-21 5-12 5 14 28 IGHG1 1-5 3 18T2_073 non-cluster III 3-33 3-22 6 18 12 IGHM 1-5 1 3 1.99E-09 NA

    Pf exposure: I, II, III, C correspond to first, second, third and challenge exposure respectivelyclr: clusterND: Not determinedCDR3 lengths are in amino acidsSHMs are counted in nucleotide base pairsTwo independent affinity (KD) measurements are called measurement 1 and 2.

    HC

    DR

    3Le

    ngth

    (aa)

    Kd (

    M)

    Mea

    sure

    men

    t1

    Kd (

    M)

    Mea

    sure

    men

    t2

    Pf s

    pzin

    hibi

    tion

    (%)

    Murugan_aap8029_Supplementary_Material_revised.pdfMurugan_Supplement figures and legends updatedSupplementary tables and algorithm combinedTable S1 and S2 CSP memory B cells and Plasmablasts countTable S3 Clonally expanded CSP memory B cell clustersmodel_parameters_20180123_newNoModel_SI_texts_20180123_newNomodel_algorithmTable S5 KCDRF8 antibodies