Intestinal CD11b(+) B Cells Ameliorate Colitis by Secreting Immunoglobulin A

The intestinal mucosal immune environment requires multiple immune cells to maintain homeostasis. Although intestinal B cells are among the most important immune cells, little is known about the mechanism that they employ to regulate immune homeostasis. In this study, we found that CD11b(+) B cells significantly accumulated in the gut lamina propria and Peyer's patches in dextran sulfate sodium-induced colitis mouse models and patients with ulcerative colitis. Adoptive transfer of CD11b(+) B cells, but not CD11b(-/-) B cells, effectively ameliorated colitis and exhibited therapeutic effects. Furthermore, CD11b(+) B cells were found to produce higher levels of IgA than CD11b(-) B cells. CD11b deficiency in B cells dampened IgA production, resulting in the loss of their ability to ameliorate colitis. Mechanistically, CD11b(+) B cells expressed abundant TGF-beta and TGF-beta receptor II, as well as highly activate phosphorylated Smad2/3 signaling pathway, consequently promoting the class switch to IgA. Collectively, our findings demonstrate that CD11b(+) B cells are essential intestinal suppressive immune cells and the primary source of intestinal IgA, which plays an indispensable role in maintaining intestinal homeostasis.