T-bet+CD11c+B cells are critical for anti-chromatin IgG production in the development of lupus

A hallmark of systemic lupus erythematosus is high titers of circulating autoantibody. A novel CD11c + B cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c + B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with great autoantibody production. In the present study we investigated the role of CD11c + B cells in the pathogenesis of lupus in the cGVHD model. Here, we found the percentage and absolute number of CD11c + B cells and titer of sera anti-chromatin IgG and IgG2a antibody were increased in cGVHD mice. CD11c + plasma cells from cGVHD mice produced large amounts of anti-chromatin IgG2a upon stimulation. Depletion of CD11c + B cells reduced anti-chromatin IgG and IgG2a production. T-bet expression was further shown to be upregulated in CD11c + B cells. Knockout of T-bet in B cells alleviated cGVHD. The percentage of T-bet + CD11c + B cells was elevated in lupus patients and positively correlated with serum anti-chromatin levels. Our findings suggest T-bet + CD11c + B cells contribute to the pathogenesis of lupus and provides potential target for therapeutic intervention.