Home LiteratureArticle Details
PMID: 20818374 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Oligomeric organization of the B-cell antigen receptor on resting cells.

Nature ·Vol. 467 ·No. 7314 ·2010-09-23 ·Pages 465-9

Yang J, Reth M

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.

MeSH Terms
Animals B-Lymphocytes/cytology,immunology,metabolism Cell Line Drosophila melanogaster/cytology Immunoglobulin D/genetics,immunology Lymphocyte Activation/immunology Protein Multimerization/immunology Receptors, Antigen, B-Cell/antagonists & inhibitors,chemistry,immunology,metabolism
Chemicals
Immunoglobulin D Receptors, Antigen, B-Cell
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Yang Jianying
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
References (31)
31 references, click to expand
  1. The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer.
    Nat Immunol. 2005 Nov;6(11):1168-76 PMID: 16200067
  2. Monomeric and oligomeric complexes of the B cell antigen receptor.
    Immunity. 2000 Jul;13(1):5-14 PMID: 10933390
  3. Antigen receptor function in chronic lymphocytic leukemia B cells.
    Leuk Lymphoma. 1996 Dec;24(1-2):27-33 PMID: 9049959
  4. Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer.
    Cell. 2004 Jun 11;117(6):787-800 PMID: 15186779
  5. Defective assembly of the B-cell receptor chains accounts for its low expression in B-chronic lymphocytic leukaemia.
    Br J Haematol. 2002 Sep;118(4):976-85 PMID: 12199775
  6. Simultaneous visualization of multiple protein interactions in living cells using multicolor fluorescence complementation analysis.
    Nat Biotechnol. 2003 May;21(5):539-45 PMID: 12692560
  7. B cell receptor signaling in human systemic lupus erythematosus.
    Curr Opin Rheumatol. 2006 Sep;18(5):451-5 PMID: 16896281
  8. Monovalent ligation of the B cell receptor induces receptor activation but fails to promote antigen presentation.
    Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3327-32 PMID: 16492756
  9. Independent trafficking of Ig-alpha/Ig-beta and mu-heavy chain is facilitated by dissociation of the B cell antigen receptor complex.
    J Immunol. 2005 Jul 1;175(1):147-54 PMID: 15972641
  10. Conventional light chains inhibit the autonomous signaling capacity of the B cell receptor.
    Immunity. 2007 Mar;26(3):323-33 PMID: 17331747
  11. The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor.
    Immunity. 2010 Feb 26;32(2):187-99 PMID: 20171124
  12. Identification of disulfide bonds in the Ig-alpha/Ig-beta component of the B cell antigen receptor using the Drosophila S2 cell reconstitution system.
    Int Immunol. 2006 Sep;18(9):1385-96 PMID: 16877534
  13. Full activation of the T cell receptor requires both clustering and conformational changes at CD3.
    Immunity. 2007 Jan;26(1):43-54 PMID: 17188005
  14. Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation.
    Cell. 2002 Jun 28;109(7):901-12 PMID: 12110186
  15. Bimolecular fluorescence complementation (BiFC) analysis as a probe of protein interactions in living cells.
    Annu Rev Biophys. 2008;37:465-87 PMID: 18573091
  16. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response.
    J Exp Med. 2005 Aug 15;202(4):493-503 PMID: 16087711
  17. Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop.
    Mol Cell. 2002 Nov;10(5):1057-69 PMID: 12453414
  18. New insights into the early molecular events underlying B cell activation.
    Immunity. 2008 May;28(5):609-19 PMID: 18482567
  19. Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells.
    Leukemia. 1997 Nov;11(11):1921-8 PMID: 9369427
  20. B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor.
    Annu Rev Immunol. 2003;21:841-94 PMID: 12615894
  21. ITAM-mediated tonic signalling through pre-BCR and BCR complexes.
    Nat Rev Immunol. 2006 Apr;6(4):283-94 PMID: 16557260
  22. TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation.
    Nat Immunol. 2010 Jan;11(1):90-6 PMID: 20010844
  23. The B-cell antigen receptor of the five immunoglobulin classes.
    Nature. 1991 Aug 29;352(6338):777-81 PMID: 1881434
  24. High-sensitivity detection and quantitative analysis of native protein-protein interactions and multiprotein complexes by flow cytometry.
    Sci STKE. 2007 Jun 05;2007(389):pl2 PMID: 17551170
  25. Viewing the antigen-induced initiation of B-cell activation in living cells.
    Immunol Rev. 2008 Feb;221:64-76 PMID: 18275475
  26. Altered T and B lymphocyte signaling pathways in lupus.
    Autoimmun Rev. 2009 Jan;8(3):179-83 PMID: 18721908
  27. The Ig-alpha ITAM is required for efficient differentiation but not proliferation of pre-B cells.
    Eur J Immunol. 2007 Jan;37(1):252-60 PMID: 17163454
  28. Conformational plasticity and navigation of signaling proteins in antigen-activated B lymphocytes.
    Adv Immunol. 2008;97:251-81 PMID: 18501772
  29. Activation of extracellular signal-regulated kinase through B-cell antigen receptor in B-cell chronic lymphocytic leukemia.
    Int J Hematol. 2002 Jun;75(5):508-13 PMID: 12095152
  30. Oligomeric antigen receptors: a new view on signaling for the selection of lymphocytes.
    Trends Immunol. 2001 Jul;22(7):356-60 PMID: 11429318
  31. Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation.
    Mol Cell. 2002 Apr;9(4):789-98 PMID: 11983170
Article Info
Journal
Nature
Abbr.
Nature
ISSN
1476-4687
Published
2010-09-23
Epub
2010-00-05
Pages
465-9
Language
English
Region
England
NLM ID
0410462
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com