T-bet+CD11c+ B cells are critical for antichromatin immunoglobulin G production in the development of lupus

• Main Authors: Ya Liu, Shiyu Zhou, Jie Qian, Yan Wang, Xiang Yu, Dai Dai, Min Dai, Lingling Wu, Zhuojun Liao, Zhixin Xue, Jiehua Wang, Goujun Hou, Jianyang Ma, John B. Harley, Yuanjia Tang, Nan Shen
• Format: Article
• Language: English
• Published: BMC 2017-10-01
• Series: Arthritis Research & Therapy
• Subjects: Systemic lupus erythematosus; Chronic graft-versus-host disease; B cell; Antichromatin antibody; T-bet
• Online Access: http://link.springer.com/article/10.1186/s13075-017-1438-2

Abstract Background A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently, 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 high autoantibody production. The purpose of this study was to explore the role of CD11c+ B cells in the pathogenesis of lupus in cGVHD mice. Methods cGVHD was induced by an intraperitoneal injection of 5 × 107 Bm12 splenocytes into B6 mice. Flow cytometry was used to analyze mice splenocytes and human samples. Magnetic beads were used to isolate mice B cells. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in serum and supernatants. Results The percentage and absolute number of CD11c+ B cells was increased in cGVHD-induced lupus, with elevated levels of antichromatin immunoglobulin (Ig)G and IgG2a in sera. CD11c+ plasma cells from cGVHD mice produced large amounts of antichromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced antichromatin IgG and IgG2a production. T-bet was upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD-induced lupus. Importantly, the percentage of T-bet+CD11c+ B cells increased in lupus patients and positively correlated with serum antichromatin levels. Conclusion T-bet+CD11c+ B cells promoted high antichromatin IgG production in the lupus-like disease model cGVHD. In lupus patients, the percentage of T-bet+CD11c+ B cells was elevated and positively correlated with antichromatin antibodies. The findings provide potential therapeutic insight into lupus disease treatment.