Anatomically remote education of B cells is required for colonic health

Mucosa-associated lymphoid tissues contain roughly 80% of all immune cells and produce virtually all of the bodys IgA1-3. Although the majority of IgA-secreting cells educated within a mucosal site home back to the same anatomic region, some cells are also found in distant mucosal tissues2-6. These observations underlie the notion of a common mucosal immune system, which holds that anatomically unrelated mucosal sites are functionally connected by a shared immune system2,3. However, the ontological basis of this separation between site of immune education and functionality has remained elusive. Here we show that mice lacking Peyers patches (PPs)--small-intestinal lymphoid tissue covered by antigen-sampling M cells--have no immunologic defect in the small-intestinal lamina propria. Surprisingly, the primary immunological abnormality in PP-deficient mice was a reduction in colonic B cells, including plasmablasts but not plasma cells. Adoptive transfer experiments conclusively demonstrated that PP-derived cells preferentially give rise to colonic--but not small-intestinal--B cells and plasmablasts. Finally, these PP-derived colonic B cells were critical for restraining colonic inflammation. Thus, PPs bridge the small-intestinal and colonic immune systems and provide a clear example of immune education being required in an anatomic compartment distinct from the effector site. Our findings, which highlight that the majority of fecal IgA is produced by colonic plasmablasts that originate from PPs, will help inform design of mucosal vaccines.