Galectin-9 regulates the threshold of B cell activation and autoimmunity

Despite the mechanisms of central and peripheral tolerance, mature B cell compartment contains cells reactive for self-antigen. How these are poised not to respond that restrain responses low-affinity endogenous antigens fully understood. Here, we demonstrate a critical role glycan-binding protein galectin-9 in setting threshold activation loss this regulatory network is sufficient drive spontaneous autoimmunity. We further restraining only conventional B-2 cells, but also innate-like B-1a cells. show galectin-9-deficient mice have an expanded population increased titers B-1a-derived autoantibodies. Mechanistically, regulates BCR distinct TLR B-1b by regulating interaction between TLRs with molecules CD5 CD180, respectively. In absence galectin-9, more readily activated secrete autoantibodies facilitate autoantigen delivery spleen, driving autoimmune responses.