| First Author | Minguet S | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 10 | Pages | 1150-1159 |
| PubMed ID | 28805811 | Mgi Jnum | J:258712 |
| Mgi Id | MGI:6140548 | Doi | 10.1038/ni.3813 |
| Citation | Minguet S, et al. (2017) Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance. Nat Immunol 18(10):1150-1159 |
| abstractText | 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-mu 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. |
