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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Caveolin-1 依赖性 BCR 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区室化。在这里，我们发现 Cav1 控制 B 细胞表面同种型特异性 B 细胞抗原受体 (BCR) 纳米簇的分布。在用抗原刺激的成熟 B 细胞中，免疫球蛋白 M BCR (IgM-BCR) 通过依赖于 Src 激酶家族对 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-BCR 和 IgD-BCR 纳米簇重组可调节体内 BCR 信号传导。在未成熟的 Cav1 缺陷 B 细胞中，IgM-BCR 纳米级组织的改变导致受体编辑失败，以及表达具有多反应性和自身反应性特征的免疫球蛋白-μ 重链的 B 细胞的偏差，最终导致自身免疫在小鼠中。因此，Cav1 作为一种细胞内在调节因子出现，通过其在质膜组织中的作用来防止 B 细胞诱导的自身免疫。