Regulatory B cells (Breg cells) help to prevent excessive tissue damage during inflammation by the production of IL-10, but the drivers of Breg cell generation have yet to be delineated. In Nature Medicine, Rosser et al. show that gut microbiota contribute to the differentiation of splenic B cells into Breg cells. Antibiotic-treated mice have fewer IL-10-producing Breg cells. In vitro stimulation with antibody to the costimulatory receptor CD40, IL-6 or IL-1β, alone or in combination, induces B cell proliferation and IL-10 production. Chimeric mice lacking B cell expression of the cytokine receptors IL-6R or IL-1R1 have not only fewer Breg cells but also defects in suppressing inflammatory arthritic disease. These findings suggest that gut microbes induce a proinflammatory response that feeds back onto splenic B cells to induce their conversion to the Breg cell phenotype.

Nat. Med. 20, 1334–1339 (2014)