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oai:repisalud.isciii.es:20.500.12105/271432026-01-15T01:20:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Minguet, Susana author Kläsener, Kathrin author Schaffer, Anna-Maria author Fiala, Gina J author Osteso-Ibánez, Teresa author Raute, Katrin author Navarro-Lérida, Inmaculada author Hartl, Frederike A author Seidl, Maximilian author Reth, Michael author Del Pozo, Miguel A author 2017-10 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. Nat Immunol. 2017 Oct;18(10):1150-1159. Nature mmunology 28805811 https://hdl.handle.net/20.500.12105/27143 Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance.