Oligomeric organization of the B-cell antigen receptor on resting cells.
B lymphocytes are activated by many different antigens to produce specific antibodies protecting higher organisms from infection. To detect its cognate antigen, each B cell contains up to 120,000 B-cell antigen receptor (BCR) complexes on its cell surface. How these abundant receptors stay silent on resting B cells and how they can be activated by a molecularly diverse set of ligands is poorly understood. Here we show, with the use of a quantitative bifluorescence complementation assay (BiFC), that the BCR has an intrinsic ability to form oligomers on the surface of living cells. A BCR mutant that fails to form oligomers is more active and cannot be expressed stably on the B-cell surface, whereas BiFC-stabilized BCR oligomers are less active and more strongly expressed on the surface. We propose that oligomers are the autoinhibited form of the BCR and that it is the shift from closed BCR oligomers to clustered monomers that drives B-cell activation in a way that is independent of the structural input from the antigen.
Yang
Jianying
J
Centre for Biological Signalling Studies BIOSS, Albert-Ludwigs-Universität Freiburg, Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs-Universität Freiburg and Max Planck Institute for Immunobiology, Stübeweg 51, 79108 Freiburg, Germany.
Reth
Michael
M
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004331:Drosophila melanogaster / Q000166:cytology; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D055503:Protein Multimerization / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*
D007072:Immunoglobulin D; D011947:Receptors, Antigen, B-Cell
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