| First Author | Raso F | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 10 | Pages | 2373-2387.e8 |
| PubMed ID | 37714151 | Mgi Jnum | J:352780 |
| Mgi Id | MGI:7540274 | Doi | 10.1016/j.immuni.2023.08.018 |
| Citation | Raso F, et al. (2023) Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation. Immunity 56(10):2373-2387.e8 |
| abstractText | Immunoglobulin A (IgA) maintains commensal communities in the intestine while preventing dysbiosis. IgA generated against intestinal microbes assures the simultaneous binding to multiple, diverse commensal-derived antigens. However, the exact mechanisms by which B cells mount broadly reactive IgA to the gut microbiome remains elusive. Here, we have shown that IgA B cell receptor (BCR) is required for B cell fitness during the germinal center (GC) reaction in Peyer's patches (PPs) and for generation of gut-homing plasma cells (PCs). We demonstrate that IgA BCR drove heightened intracellular signaling in mouse and human B cells, and as a consequence, IgA(+) B cells received stronger positive selection cues. Mechanistically, IgA BCR signaling offset Fas-mediated death, possibly rescuing low-affinity B cells to promote a broad humoral response to commensals. Our findings reveal an additional mechanism linking BCR signaling, B cell fate, and antibody production location, which have implications for how intestinal antigen recognition shapes humoral immunity. |
