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Complete sequence and gene maps of bothhuman and chicken major histocompat-ibility complex (MHC) regions have re-cently been reported. The MHCs of chickensand humans differ in their size, organiza-tion, complexity and evolution.

The human HLA region comprises 224genes in 3.6 mb of DNA. Of these, 128 arepredicted to be functional and 96 arepseudogenes. It is estimated that 40% of the expressed genes play a role in the immune system. By contrast, the chickenMHC (called the B locus) is 92 kb in size,contains only 19 genes, and the class III region genes are located outside the class Iand II region genes. Unexpectedly, protea-some (LMP) genes are absent from thechicken MHC. This feature might help explain why acidic residues are often pre-sent at the C-terminus of peptides that bind to chicken classical class I molecules. In humans, which possess proteasomegenes in their MHC, hydrophobic or basic

residues are preferentially located at the C-terminus.

Another unusual feature of the chickenMHC is the presence of two genes encodingC-type lectins, which resemble the lectin-like natural killer (NK) receptors of mammals.Kaufman et al. speculate that the presence ofthese genes in the MHC region might ex-plain the association of the chicken MHCand susceptibility to infection by the herpesvirus that causes Marek’s disease.

In terms of evolution, the human andchicken MHCs couldn’t be more different.The size and complexity of the human MHCregion permits meiotic recombination tooccur resulting in the generation of newMHC haplotypes, whereas the chickenMHC region is small and compact such thatmeiotic recombination is unlikely to occur,and the co-evolution of MHC genes leads tostable haplotypes.

Elaine Bell

What are the molecular switches that control lineage commitment of commonlymphoid progenitor (CLP) cells? For Bcells, it is known that lineage commitmentcannot be initiated without two transcrip-tion factors, E2A and EBF (early B-cell fac-tor). Using Pax5-knockout (Pax52/2) mice,Nutt and colleagues add two key pieces tothis jigsaw.

First, once initiated, pro B-cell develop-ment cannot proceed in the absence of Pax5,which encodes the B-cell-specific activatorprotein (BSAP). This is irrespective of thepresence of interleukin 7 (IL-7), which sup-ports B-cell commitment and developmentin wild-type Pro-B cells. Analysis of gene expression suggests that, in wild-type pro-Bcells, Pax5 acts to repress expression of lineage-promiscuous genes, such as macro-phage colony-stimulating factor receptor(M-CFR). Despite the failure of B-lineage

commitment, Pax52/2 pro-B cells continueto express genes for rearrangement of thepre-B-cell receptor (BCR) complex. Second,and of wider importance, in the absence ofPax5 activity pro-B cells retain the potentialto differentiate into functional macro-phages, dendritic cells, granulocytes andnatural killer cells.

This study has reshaped our under-standing of lymphoid development. Previ-ously it was assumed that ongoing attemptsto rearrange the BCR must be indicative ofB-lineage commitment – this is clearly nottrue. Moreover, the fact that Pax52/2 pro-Bcells are able to pursue alternative lymphoidlineage strategies challenges the dogma thatintermediate lymphoid progenitor stageshave a restricted developmental potentialcompared with CLP cells.

Robert Brines

Complete sequence of the human and chicken MHCThe MHC consortium (1999) Complete sequence and gene map of a human major histocom-patibility complex. Nature 401, 921–923Kaufman, J. et al. (1999) The chicken B locus is a minimal essential major histocompatibilitycomplex. Nature 401, 923–925

RTD-1: a new type of defensinTang, Y-Q. et al. (1999) A cyclic anti-microbialpeptide produced in primate leukocytes bythe ligation of two truncated a-defensins. Science 286, 498–502

Innate immune mechanisms exist to providean immediate response to microbial infec-tion. Recent studies have revealed that innate defense mechanisms are remarkablyconserved across species and exhibit somedegree of specificity. Anti-microbial pep-tides, of which the defensins are one class,constitute a major component of innate de-fense, particularly in plants and insects. Vertebrate defensins, which fall into twostructural classes a and b, are cationic mol-ecules which act by preferentially disruptingmicrobial membranes.

A recent paper in Science describes theisolation of a novel anti-microbial peptidefrom rhesus macaque neutrophils andmonocytes, termed rhesus theta defensin 1(RTD-1). The cyclical structure of this pep-tide, which more closely resembles porcineprotegrins, is unique among defensins andconfers increased microbicidal activity com-pared with an acyclic form. The peptide isformed by the ligation of two truncated a-defensin nonapeptides in a head-to-tailmanner. The post-translational mechanismwhich leads to the formation of RTD-1 hasnot previously been recognized and requiresfurther characterization. Like protegrins, butunlike other defensins, the microbicidal ac-tivity of RTD-1 is resistant to increased saltconcentration. This feature of RTD-1, whichenables it to retain functional activity at thesalt concentrations present in blood, makesit an attractive candidate for the develop-ment of therapeutic compounds to replaceexisting antibiotics.

Elaine Bell

To B or not to B: Pax5 in B-cell developmentNutt, S.L. et al. (1999) Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401, 556–562

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