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研究揭示六类免疫疾病中的B细胞受体库
2019-09-26 14:21

英国剑桥大学K. G. C. Smith和R. J. M. Bashford-Rogers等研究人员,合作完成了对六种免疫介导疾病中B细胞受体(BCR)组成的分析。相关论文,2019年9月25日在线发表于国际学术期刊《自然》。

研究人员通过分析BCR克隆以及免疫球蛋白重链可变区(IGHV)基因的使用,尤其是同种型的使用,比较了系统性红斑狼疮、抗中性粒细胞胞浆抗体(ANCA)相关血管炎、克罗恩氏病、贝塞奇氏病、具有多血管炎的嗜酸性肉芽肿以及免疫球蛋白A(IgA)血管炎。以IgA亚型为主的系统性红斑狼疮和克罗恩氏病的克隆性增加,以及在这些疾病和其他疾病中IGHV基因的偏向使用,提示微生物对发病机理的贡献。不同的免疫抑制治疗对BCR库具有特定而独特的影响。利妥昔单抗治疗后持续存在的B细胞主要是同种型转换并克隆扩增,而霉菌酚酸酯治疗后持续存在的B细胞则相反。

研究人员对免疫介导的疾病中BCR组成部分的比较分析揭示了复杂的B细胞结构,为理解病理机制和设计治疗策略提供了平台。

据悉,B细胞在许多(甚至可能是全部)免疫介导的疾病的发病机理中都很重要。每个B细胞都表达一个BCR,并且个体的总B细胞群体所表达的各种BCR称为“ BCR库”。我们对免疫介导的疾病背景下的BCR库的理解还不完整,对此进行定义可以为发病机理和治疗方法提供新的见解。

附:英文原文

Title: Analysis of the B cell receptor repertoire in six immune-mediated diseases

Author: R. J. M. Bashford-Rogers, L. Bergamaschi, E. F. McKinney, D. C. Pombal, F. Mescia, J. C. Lee, D. C. Thomas, S. M. Flint, P. Kellam, D. R. W. Jayne, P. A. Lyons, K. G. C. Smith

Issue&Volume: 2019-09-25

Abstract: 

B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Each B cell expresses a single B cell receptor (BCR)1, and the diverse range of BCRs expressed by the total B cell population of an individual is termed the ‘BCR repertoire’. Our understanding of the BCR repertoire in the context of immune-mediated diseases is incomplete, and defining this could provide new insights into pathogenesis and therapy. Here, we compared the BCR repertoire in systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Crohn’s disease, Behçet’s disease, eosinophilic granulomatosis with polyangiitis, and immunoglobulin A (IgA) vasculitis by analysing BCR clonality, use of immunoglobulin heavy-chain variable region (IGHV) genes and—in particular—isotype use. An increase in clonality in systemic lupus erythematosus and Crohn’s disease that was dominated by the IgA isotype, together with skewed use of the IGHV genes in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatments had specific and distinct effects on the repertoire; B cells that persisted after treatment with rituximab were predominately isotype-switched and clonally expanded, whereas the inverse was true for B cells that persisted after treatment with mycophenolate mofetil. Our comparative analysis of the BCR repertoire in immune-mediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.

DOI: 10.1038/s41586-019-1595-3

Source:https://www.nature.com/articles/s41586-019-1595-3

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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