{Reference Type}: Journal Article
{Title}: Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation.
{Author}: Raso F;Liu S;Simpson MJ;Barton GM;Mayer CT;Acharya M;Muppidi JR;Marshak-Rothstein A;Reboldi A;
{Journal}: Immunity
{Volume}: 56
{Issue}: 10
{Year}: 2023 10 10
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2023.08.018
{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.