3 years ago

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

Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance
Miguel A Del Pozo, Frederike A Hartl, Maximilian Seidl, Michael Reth, Kathrin Kläsener, Teresa Osteso-Ibánez, Gina J Fiala, Katrin Raute, Anna-Maria Schaffer, Susana Minguet, Inmaculada Navarro-Lérida
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.

Publisher URL: http://dx.doi.org/10.1038/ni.3813

DOI: 10.1038/ni.3813

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