T-bet+ CD11c+ B cells are critical for anti-chromatin IgG production in the development of lupus
| Autor: | Jie Qian, Min Dai, Goujun Hou, Yan Wang, Xiang Yu, John B. Harley, Nan Shen, Zhixin Xue, Zhuojun Liao, Lingling Wu, Ya Liu, Jiehua Wang, Shiyu Zhou, Jianyang Ma, Yuanjia Tang, Dai Dai |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Systemic lupus erythematosus
Autoantibody CD11c hemic and immune systems chemical and pharmacologic phenomena Biology medicine.disease medicine.disease_cause Autoimmunity Pathogenesis Titer medicine.anatomical_structure Downregulation and upregulation immune system diseases Immunology medicine B cell |
| DOI: | 10.1101/116145 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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