Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients  

作　　者：Mei Liu Qiang Guo Chunmei Wu Delphine Sterlin Shyamal Goswami Ying Zhang Teng Li Chunde Bao Nan Shen Qiong Fu Xiaoming Zhang 

机构地区：[1]Key Laboratory of Molecular Virology&Immunology,Institut Pasteur of Shanghai,Chinese Academy of Sciences/University of Chinese Academy of Sciences,Shanghai 200031,China [2]Department of Rheumatology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200001,China

出　　处：《Cellular & Molecular Immunology》2019年第4期367-379,共13页中国免疫学杂志（英文版）

基　　金：This work was supported by the National Basic Research Program of China(No.2014CB541904);the National Natural Science Foundation of China(Nos.31470879 81571575 8171101311 and 31770960);the Interdisciplinary Innovation Team,External Cooperation Program(No.GJHZ201312);Key Project QYZDB-SSW-SMC036;the Strategic Priority Research Program(No.XDPB0303),Chinese Academy of Sciences.

摘　　要：A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.

关 键 词：Systemic lupus erythematosus type I interferons transitional B cells APOPTOSIS interleukin 6 

分 类 号：R59[医药卫生—内科学]