Abstract
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.
Footnotes
Supported by the National Basic Research Program of China (973 program, grants 2014CB541902 and 2014CB541901), the National Natural Science Foundation of China (grants 81230072, 31630021, 31370880, 81571576, 81401331 and 81571588), the Key Research Program of Bureau of Frontier Sciences and Education Chinese Academy of Sciences (grant QYZDJ-SSW-SMC006), and the Key Research Program of the Chinese Academy of Sciences (grant KJZD-EW-L01-3).
The authors have no conflicting financial interests.