I27-Breg cells

Importance of regulatory B cells (Breg cells) is underscored by scores of autoimmune, infectious, or neoplastic diseases that result from loss of Breg functions in vivo. We identified an innate B-1a Breg population in peritoneal cavity and human umbilical cord that suppresses encephalomyelitis or uveitis by propagating inhibitory signals that convert conventional lymphocytes to IL-35–secreting regulatory cells and inhibiting Lag3 + PD-1 + T cells that mediate CNS autoimmune diseases. Furthermore, IRF8 signaling is required for i27-Breg development and loss of IL-27Rα or IL-27 function in B cells abrogates capacity of i27-Bregs to suppress diseases or induce B-1a differentiation into i27-Breg. i27-Breg requires activation by innate stimuli and is not antigen-specific, suggesting that i27-Breg would be effective immunotherapy for diverse autoimmune diseases.