RT Journal Article
SR Electronic
T1 T-bet+ CD11c+ B cells are critical for anti-chromatin IgG production in the development of lupus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 116145
DO 10.1101/116145
A1 Ya Liu
A1 Shiyu Zhou
A1 Jie Qian
A1 Yan Wang
A1 Xiang Yu
A1 Dai Dai
A1 Min Dai
A1 Lingling Wu
A1 Zhuojun Liao
A1 Zhixin Xue
A1 Jiehua Wang
A1 Guojun Hou
A1 Jianyang Ma
A1 John B. Harley
A1 Yuanjia Tang
A1 Nan Shen
YR 2017
UL http://biorxiv.org/content/early/2017/03/12/116145.abstract
AB 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.