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Current literature

Two novel members of the B7 family,murine B7h and human B7-H1, have re-cently been identified. B7h was identifiedusing a subtractive screen designed to isolate tumour necrosis factor a (TNF-a)-induced genes that are specifically regu-lated by NF-kB/Rel transcription factors,whereas B7-H1 was identified by searchingan EST database for homologues of B7-1 andB7-2.

The classic costimulatory molecules, B7-1and B7-2, are constitutively expressed ondendritic cells and upregulated after activa-tion on monocytes, macrophages, and B andT cells. B7h is expressed on antigen-present-ing cells (APCs) but can also be expressedon other cell types in response to TNF stim-ulation. The inducible expression of B7h onnon-APCs and the higher threshold of T-cellreceptor activation required for costimula-tion via B7h, suggest a distinct functional

role for B7h compared with B7-1 and B7-2.The authors speculate that instead of co-stimulating naive T cells, B7h may influencelocal tissue responses by costimulating T cells following their primary activation inlymph nodes.

Both B7h and B7-H1 stimulate T-cell pro-liferation independent of CD28 and CTLA-4.However, B7h may interact with ICOS, a re-cently described homologue of CD28 andCTLA-4. B7-H1 also stimulates T-cell prolif-eration and increases cytokine secretion, especially interleukin 10 (IL-10); IL-2, although produced in small amounts, is necessary for B7-H1 costimulation. The datafrom these two papers suggest that, in con-trast to B7-1 and B7-2, the newer membersof the family might act as negative regulatorsof cellular immune responses.

Elaine Bell

Natural antibodies: directingpathogen distributionOchsenbein, A.F. et al. (1999) Control of earlyviral and bacterial distribution and disease bynatural antibodies. Science 286, 2156–2159

Natural antibodies produced by B cells con-tribute to the humoral response, however,their role in host defence is not yet fully understood. In a recent article in Science,Ochsenbein and colleagues show that natu-ral antibodies are important in preventingvirus dissemination and in targeting virus tosecondary lymphoid organs – thus helpingto enhance the immune response.

Natural antibodies from sera of naivemice were shown to be specific for certainpathogens. When mice lacking these anti-bodies were infected with virus or bacteria,titres of pathogen in the blood and periph-eral organs, such as the liver, kidney andbrain, were found to be 10–100 times higherthan those in antibody-producing mice. Bycontrast, viral or bacterial titres in secondarylymphoid organs such as the spleen of antibody-deficient mice were 10–100 timeslower than levels in normal mice. Subse-quently, when mouse serum containingnatural antibodies was added to antibody-deficient mice, viral titres in the peripheralorgans decreased and viral titres in thespleen increased.

Thus, natural antibodies appear to play akey role not only in preventing pathogendissemination to vital target organs but alsoin enhancing the recruitment of pathogensto secondary lymphoid organs

Kirsty McCormack

B7h and B7-H1: new members of the B7 familySwallow, M.M. et al. (1999) B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced byTNF-a. Immunity 11, 423–432Dong, H. et al. (1999) B7-H1, a third member of the B7 family, co-stimulates T-cell proliferationand interleukin-10 secretion. Nat. Med. 5, 1365–1369

Following crosslinking with antigen, the B-cell antigen receptor (BCR) not only initiatessignal transduction but also internalizes andtargets antigen for processing and ultimatepresentation by major histocompatibilitycomplex (MHC) class II molecules. Are thesetwo separate functions coordinated and if so, how?

Here, Cheng and colleagues show that,once crosslinked, the BCR rapidly translo-cates into ganglioside GM1-enriched lipidrafts from which it is excluded in restingcells. These rafts also include the Lyn proteintyrosine kinase but exclude the phosphataseCD45R, resulting in phosphorylation of Lynand the CD79a (Iga/MB1) BCR component.The important link between B-cell activationand subsequent MHC class II presentation is revealed by the observation that, follow-ing crosslinking and phosphorylation, the BCR and a portion of GM1 remain associated

sufficiently for them to be targeted to the late class II peptide loading compartment(IIPLC). This overall process is not simplyfacilitated by the entry of the BCR into lipidrafts since targeting to the antigen processingcompartments will only occur if an intact Ig cytoplasmic domain is present, pre-sumably to stabilize the CD79a part of the complex.

These data provide evidence that GM1-rich lipid rafts play a key role linking theprocess of BCR signalling to subsequentantigen targeting for processing and pres-entation in the context of MHC class II, withkey roles assigned to each of the componentsof the BCR. This latter antigen targeting andprocessing function helps to sustain subse-quent T-cell activity and thus complete thecycle of immune activation and response.

Rob Brines

A raft of B-cell receptor activityCheng, P.C. et al. (1999) A role for lipid rafts in B cell antigen receptor signaling and antigen targeting. J. Exp. Med. 190, 1549–1560

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