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免疫球蛋白重链类别转换重组:机制与调控

IgH chain class switch recombination: mechanism and regulation.

作者信息

Stavnezer Janet, Schrader Carol E

机构信息

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605

Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605.

出版信息

J Immunol. 2014 Dec 1;193(11):5370-8. doi: 10.4049/jimmunol.1401849.

Abstract

IgH class switching occurs rapidly after activation of mature naive B cells, resulting in a switch from expression of IgM and IgD to expression of IgG, IgE, or IgA; this switch improves the ability of Abs to remove the pathogen that induces the humoral immune response. Class switching occurs by a deletional recombination between two switch regions, each of which is associated with a H chain constant region gene. Class switch recombination (CSR) is instigated by activation-induced cytidine deaminase, which converts cytosines in switch regions to uracils. The uracils are subsequently removed by two DNA-repair pathways, resulting in mutations, single-strand DNA breaks, and the double-strand breaks required for CSR. We discuss several aspects of CSR, including how CSR is induced, CSR in B cell progenitors, the roles of transcription and chromosomal looping in CSR, and the roles of certain DNA-repair enzymes in CSR.

摘要

成熟幼稚B细胞激活后,IgH类别转换迅速发生,导致表达从IgM和IgD转变为IgG、IgE或IgA;这种转换提高了抗体清除诱导体液免疫反应病原体的能力。类别转换通过两个转换区之间的缺失重组发生,每个转换区都与一个重链恒定区基因相关。类别转换重组(CSR)由激活诱导的胞苷脱氨酶引发,该酶将转换区中的胞嘧啶转化为尿嘧啶。随后,尿嘧啶通过两条DNA修复途径被去除,导致突变、单链DNA断裂以及CSR所需的双链断裂。我们讨论了CSR的几个方面,包括CSR如何被诱导、B细胞祖细胞中的CSR、转录和染色体环化在CSR中的作用以及某些DNA修复酶在CSR中的作用。

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