Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation

Immunity. 2023 Oct 10;56(10):2373-2387.e8. doi: 10.1016/j.immuni.2023.08.018. Epub 2023 Sep 14.


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.

Keywords: B cell receptor; Fas; IgA; Peyer's patch; germinal center; gut homing.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens / metabolism
  • B-Lymphocytes*
  • Humans
  • Immunoglobulin A
  • Intestinal Mucosa
  • Mice
  • Peyer's Patches*
  • Receptors, Antigen, B-Cell / metabolism


  • Antigens
  • Receptors, Antigen, B-Cell
  • Immunoglobulin A