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

Nature volume 467, pages 465–469 (2010)Cite this article

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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 understood1. Here we show, with the use of a quantitative bifluorescence complementation assay (BiFC)2,3, 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.

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Figure 1: BCR oligomers on S2 cell surface detected by BiFC and IP-FCM.
Figure 2: A double-mutant IgD–BCR complex without oligomerization.
Figure 3: Monomeric BCR is not stably expressed on the B-cell surface.
Figure 4: Oligomeric BCR is highly expressed and autoinhibited.

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Acknowledgements

We thank L. Leclercq, P. Nielsen, H. Jumaa and W. Schamel for critical reading of this manuscript. This study was supported by the Excellence Initiative of the German Federal and State Governments (EXC 294), by the Deutsche Forschungsgemeinschaft through SFB746 and by the FRISYS programme.

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Authors and Affiliations

  1. Department of Molecular Immunology, Centre for Biological Signalling Studies BIOSS, Albert-Ludwigs-Universität Freiburg, Faculty of Biology, Albert-Ludwigs-Universität Freiburg and Max Planck Institute for Immunobiology, Stübeweg 51, 79108 Freiburg, Germany,

    Jianying Yang & Michael Reth

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  1. Jianying Yang
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  2. Michael Reth
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Contributions

All experiments were planned by M.R. and J.Y. and conducted by J.Y. The manuscript was prepared by M.R. with J.Y.

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Correspondence to Michael Reth.

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The authors declare no competing financial interests.

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Yang, J., Reth, M. Oligomeric organization of the B-cell antigen receptor on resting cells. Nature 467, 465–469 (2010). https://doi.org/10.1038/nature09357

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