PDF(Pubmed)
Abstract：
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.
摘要：
免疫球蛋白A（IgA）在肠道中维持共生群落，同时防止生态失调。针对肠道微生物产生的IgA确保同时结合多个，不同的共生衍生抗原。然而,B细胞对肠道微生物组产生广泛反应性IgA的确切机制仍然难以捉摸。这里,我们已经表明，IgAB细胞受体（BCR）在生发中心（GC）反应期间的B细胞适应性在Peyer的斑块（PPs）和肠道归巢浆细胞（PC）的产生。我们证明IgABCR在小鼠和人类B细胞中驱动增强的细胞内信号传导，因此，IgA+B细胞收到更强的阳性选择线索。机械上,IgABCR信号抵消Fas介导的死亡，可能挽救低亲和力B细胞以促进对共生的广泛体液反应。我们的发现揭示了一个连接BCR信号的额外机制，B细胞命运,和抗体生产地点，这对肠道抗原识别如何塑造体液免疫有影响。
