Genetic obstacles to developing and tolerizing human B cells.

IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Kim Nguyen, N. Alsaati, Carole Le Coz, N. Romberg
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引用次数: 1

Abstract

Early in development, B cells explosively diversify B-cell receptors (BCRs) to recognize a wide variety of microbial antigens. A variety of developmental and tolerance checkpoints are subsequently deployed at later developmental stages to purge useless or potentially dangerous autoreactive B-cell clones. Once B cells recognize cognate antigens within secondary lymphoid tissues, their BCRs are genetically modified to increase the specificity and strength of antigen binding. Identification and investigation of monogenic inborn errors of immunity (IEI) diseases demonstrate which specific molecules and pathways are essential for developing well-tolerized human B cells. Although rare, IEI patients have provided important mechanistic insights into, and therapeutic clues for, patients afflicted with more common autoantibody associated autoimmune diseases like lupus, rheumatoid arthritis, and type 1 diabetes. This article is categorized under: Immune System Diseases > Stem Cells and Development > Genetics/Genomics/Epigenetics.
人类B细胞发育和耐受的遗传障碍。
在发育早期,B细胞爆炸性地使B细胞受体(BCRs)多样化,以识别多种微生物抗原。随后在发育后期部署各种发育和耐受检查点,以清除无用或潜在危险的自身反应B细胞克隆。一旦B细胞识别次级淋巴组织中的同源抗原,它们的BCR就会进行基因修饰,以增加抗原结合的特异性和强度。对单基因先天性免疫缺陷(IEI)疾病的鉴定和研究表明,哪些特定分子和途径对培养耐受性良好的人类B细胞至关重要。尽管罕见,但IEI患者为患有更常见的自身抗体相关自身免疫性疾病(如狼疮、类风湿性关节炎和1型糖尿病)的患者提供了重要的机制见解和治疗线索。本文分类如下:免疫系统疾病>干细胞与发育>遗传学/基因组学/表观遗传学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
WIREs Mechanisms of Disease
WIREs Mechanisms of Disease MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
11.40
自引率
0.00%
发文量
45
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