TY - JOUR T1 - T-bet<sup>+</sup> CD11c<sup>+</sup> B cells are critical for anti-chromatin IgG production in the development of lupus JF - bioRxiv DO - 10.1101/116145 SP - 116145 AU - Ya Liu AU - Shiyu Zhou AU - Jie Qian AU - Yan Wang AU - Xiang Yu AU - Dai Dai AU - Min Dai AU - Lingling Wu AU - Zhuojun Liao AU - Zhixin Xue AU - Jiehua Wang AU - Guojun Hou AU - Jianyang Ma AU - John B. Harley AU - Yuanjia Tang AU - Nan Shen Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/03/12/116145.abstract N2 - 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. ER -