Arthritis Research & Therapy (2017-10-01)

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

  • 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

DOI
https://doi.org/10.1186/s13075-017-1438-2
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 11

Abstract

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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.

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