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

Y Liu, S Zhou, J Qian, Y Wang, X Yu, D Dai… - Arthritis research & …, 2017 - Springer
Y Liu, S Zhou, J Qian, Y Wang, X Yu, D Dai, M Dai, L Wu, Z Liao, Z Xue, J Wang, G Hou…
Arthritis research & therapy, 2017Springer
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 …
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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