Regulatory T cells prevent the emergence of autoantibodies and excessive IgE, but the precise mechanisms are unclear. Follicular regulatory T (Tfr) cells, produce the neurotrophic factor neuritin that can directly target B cells. Mice lacking Tfr cells or neuritin in Foxp3-expressing cells accumulate early plasma cells in germinal centres (GCs) and develop autoantibodies against histones and tissue-specific antigens. Upon immunization, these mice also produce increased circulating IgE and IgG1. When taken up by B cells, neuritin dampens IgE class switching and differentiation of mouse and human B cells into plasma cells by downregulating BLIMP-1 and upregulating BCL6. Systemic administration of neuritin to Tfr-deficient mice prevented the accumulation of early plasma cells in GCs. Production of neuritin by Tfr cells emerges as a central mechanism to suppress pathogenic B cell responses.