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.

中文翻译：

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BCR的Caveolin-1依赖性纳米级组织调节B细胞耐受性

Caveolin-1（Cav1）调节质膜的纳米级组织和分隔。在这里，我们发现Cav1控制B细胞表面上同型特异性B细胞抗原受体（BCR）的纳米簇的分布。在受抗原刺激的成熟B细胞中，免疫球蛋白M BCR（IgM-BCR）通过依赖于Src激酶家族Cav1磷酸化的过程获得了富含GM1糖脂的脂质结构域。抗原诱导的IgM-BCRs和IgD-BCRs纳米簇的重组在体内调节BCR信号传导。在未成熟的Cav1缺陷B细胞中，IgM-BCRs纳米结构的改变导致受体编辑失败，表达免疫球蛋白-μ重链且具有多反应性和自身反应性的B细胞谱系偏向，最终导致自身免疫在小鼠中。因此，Cav1成为一种细胞内在调节剂，通过其在血浆膜组织中的作用阻止B细胞诱导的自身免疫。