title: Oligomeric organization of the B-cell antigen receptor on resting cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jianying
authors.initials: J
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
mesh_terms: 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*
chemical_list: D007072:Immunoglobulin D; D011947:Receptors, Antigen, B-Cell
references.citation: Nat Immunol. 2005 Nov;6(11):1168-76
references.pmid: 16200067
references.citation: Immunity. 2000 Jul;13(1):5-14
references.pmid: 10933390
references.citation: Leuk Lymphoma. 1996 Dec;24(1-2):27-33
references.pmid: 9049959
references.citation: Cell. 2004 Jun 11;117(6):787-800
references.pmid: 15186779
references.citation: Br J Haematol. 2002 Sep;118(4):976-85
references.pmid: 12199775
references.citation: Nat Biotechnol. 2003 May;21(5):539-45
references.pmid: 12692560
references.citation: Curr Opin Rheumatol. 2006 Sep;18(5):451-5
references.pmid: 16896281
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3327-32
references.pmid: 16492756
references.citation: J Immunol. 2005 Jul 1;175(1):147-54
references.pmid: 15972641
references.citation: Immunity. 2007 Mar;26(3):323-33
references.pmid: 17331747
references.citation: Immunity. 2010 Feb 26;32(2):187-99
references.pmid: 20171124
references.citation: Int Immunol. 2006 Sep;18(9):1385-96
references.pmid: 16877534
references.citation: Immunity. 2007 Jan;26(1):43-54
references.pmid: 17188005
references.citation: Cell. 2002 Jun 28;109(7):901-12
references.pmid: 12110186
references.citation: Annu Rev Biophys. 2008;37:465-87
references.pmid: 18573091
references.citation: J Exp Med. 2005 Aug 15;202(4):493-503
references.pmid: 16087711
references.citation: Mol Cell. 2002 Nov;10(5):1057-69
references.pmid: 12453414
references.citation: Immunity. 2008 May;28(5):609-19
references.pmid: 18482567
references.citation: Leukemia. 1997 Nov;11(11):1921-8
references.pmid: 9369427
references.citation: Annu Rev Immunol. 2003;21:841-94
references.pmid: 12615894
references.citation: Nat Rev Immunol. 2006 Apr;6(4):283-94
references.pmid: 16557260
references.citation: Nat Immunol. 2010 Jan;11(1):90-6
references.pmid: 20010844
references.citation: Nature. 1991 Aug 29;352(6338):777-81
references.pmid: 1881434
references.citation: Sci STKE. 2007 Jun 05;2007(389):pl2
references.pmid: 17551170
references.citation: Immunol Rev. 2008 Feb;221:64-76
references.pmid: 18275475
references.citation: Autoimmun Rev. 2009 Jan;8(3):179-83
references.pmid: 18721908
references.citation: Eur J Immunol. 2007 Jan;37(1):252-60
references.pmid: 17163454
references.citation: Adv Immunol. 2008;97:251-81
references.pmid: 18501772
references.citation: Int J Hematol. 2002 Jun;75(5):508-13
references.pmid: 12095152
references.citation: Trends Immunol. 2001 Jul;22(7):356-60
references.pmid: 11429318
references.citation: Mol Cell. 2002 Apr;9(4):789-98
references.pmid: 11983170