Data indicate a role for TGF-β1 expression in regulatory B cell functions, although this mechanism has not been tested in autoimmune neuroinflammation. Transgenic mice deficient for TGF-β1 expression in B cells (B–TGF-β1–/–) were tested in EAE induced by recombinant mouse MOG (rmMOG) or adoptive transfer EAE (at-EAE). In rmMOG EAE, B–TGF-β1–/– mice showed an earlier disease onset compared to littermate controls. Exacerbated EAE susceptibility was associated with augmented CNS T helper cell responses. Additionally, selective B cell TGF-β1–deficiency increased the frequencies and activation of myeloid DCs. Lack of TGF-β1 production by B cells did not influence the EAE course in at-EAE. Collectively our data suggest that in rmMOG EAE B cells can regulate the function of APCs, and in turn encephalitogenic Th1/17 responses, via TGF-β1. An in vitro study of human B cells further indicated that TGF-β1 is downregulated when B cells are activated.