Background and aims A hallmark of systemic lupus erythematosus is high titers of circulating autoantibodies. Recently a novel CD11c+ B cell subset has been identified in aged female mice that is critical for the development of autoimmunity.Transfer of MHC II-mismatched splenocytes from Bm12 mice into B6 mice causes a chronic graft versus host reaction (cGVHD), which is characterised by the production of high titers of autoantibodies and immunopathology that closely resemble SLE. The aim of this study was to figure out the role of CD11c+ B cell in the production of autoantibodies during the development of lupus induced by cGVHD.
Methods We developed and validated cGVHD model by splenocytes transfer of Bm12 mice into B6 mice and identified CD11c+ B cell by flow cytometry and examined anti-chromatin antibody by ELISA. We also identified CD11c+T-bet+ B cell of peripheral blood mononuclear cells obtained from SLE patients and healthy controls.
Results CD11c+T-bet+ B cell was significantly increased in the development of lupus induced by cGVHD. CD138+CD11c+ B cell produced large amounts of anti-chromatin IgG2a upon in vitro stimulation. Depletion of CD11c+ B cells significantly ameliorated anti-chromatin IgG2a production in vivo. T-bet deficiency impaired the expression of CD11c in B cells and anti-chromatin autoantibodies production in the process of cGVHD. The accumulation of T-bet+CD11+ B cell was found in lupus patients.
Conclusions Our data demonstrated the aberrant activation and differentiation of CD11c+T-bet+ B cell, which produced large amounts of anti-chromatin IgG2a in lupus murine model and patients.
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