期刊
NATURE
卷 574, 期 7776, 页码 122-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-1595-3
关键词
-
资金
- Wellcome Trust [WT106068AIA, 083650/Z/07/Z]
- EU [733100]
- UK Medical Research Council [MR/L019027]
- UK National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre
- MRC [MR/L019027/1] Funding Source: UKRI
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, Behcet'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 immun o suppressive 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 immunemediated disease reveals a complex B cell architecture, providing a platform for understanding pathological mechanisms and designing treatment strategies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据