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Journal Article

Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance

MPS-Authors

Kläsener,  Kathrin
Department of Immunology, University of Freiburg;
Centre for Biological Signalling Studies BIOSS, University of Freiburg;
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Reth,  Michael
Department of Immunology, University of Freiburg;
Centre for Biological Signalling Studies BIOSS, University of Freiburg;
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Minguet, S., Kläsener, K., Schaffer, A.-M., Fiala, G. J., Osteso-Ibánez, T., Raute, K., et al. (2017). Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance. Nature Immunology, 18, 1150-1159. doi:10.1038/ni.3813.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002E-8579-A
Abstract
Caveolin-1 (Cav1) regulates the nanoscale organization and compartmentalization of the plasma membrane. Here we found that Cav1 controlled the distribution of nanoclusters of isotype-specific B cell antigen receptors (BCRs) on the surface of B cells. In mature B cells stimulated with antigen, the immunoglobulin M BCR (IgM-BCR) gained access to lipid domains enriched for GM1 glycolipids, by a process that was dependent on the phosphorylation of Cav1 by the Src family of kinases. Antigen-induced reorganization of nanoclusters of IgM-BCRs and IgD-BCRs regulated BCR signaling in vivo. In immature Cav1-deficient B cells, altered nanoscale organization of IgM-BCRs resulted in a failure of receptor editing and a skewed repertoire of B cells expressing immunoglobulin-μ heavy chains with hallmarks of poly- and auto-reactivity, which ultimately led to autoimmunity in mice. Thus, Cav1 emerges as a cell-intrinsic regulator that prevents B cell-induced autoimmunity by means of its role in plasma-membrane organization.