T-bet+ CD11c+ B Cells Are Critical For Anti-Chromatin IgG Production In The Development Of Lupus

Liu, Y.; Zhou, S.; Qian, J.; Wang, Y.; Yu, X.; Dai, D.; Dai, M.; Wu, L.; Liao, Z.; Xue, Z.; Wang, J.; Hou, G.; Ma, J.; Harley, J. B.; Tang, Y.; Shen, N.

doi:10.1101/116145

bioRxiv · 10.1101/116145

T-bet+ CD11c+ B Cells Are Critical For Anti-Chromatin IgG Production In The Development Of Lupus

Liu, Y.·Zhou, S.·Qian, J.·Wang, Y.·Yu, X.·Dai, D.·Dai, M.·Wu, L.·Liao, Z.·Xue, Z.·Wang, J.·Hou, G.·Ma, J.·Harley, J. B.·Tang, Y.·Shen, N.

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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.

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Liu, Y., Zhou, S., Qian, J., Wang, Y., Yu, X., Dai, D., Dai, M., Wu, L., Liao, Z., Xue, Z., Wang, J., Hou, G., Ma, J., Harley, J. B., Tang, Y., Shen, N.. 2017-03-12. T-bet+ CD11c+ B Cells Are Critical For Anti-Chromatin IgG Production In The Development Of Lupus. https://doi.org/10.1101/116145

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