Current insights into the mechanism of mammalian immunoglobulin class switch recombination.

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Critical Reviews in Biochemistry and Molecular Biology Pub Date : 2019-08-01 Epub Date: 2019-09-11 DOI:10.1080/10409238.2019.1659227
Kefei Yu, Michael R Lieber
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Abstract

Immunoglobulin (Ig) class switch recombination (CSR) is the gene rearrangement process by which B lymphocytes change the Ig heavy chain constant region to permit a switch of Ig isotype from IgM to IgG, IgA, or IgE. At the DNA level, CSR occurs via generation and joining of DNA double strand breaks (DSBs) at intronic switch regions located just upstream of each of the heavy chain constant regions. Activation-induced deaminase (AID), a B cell specific enzyme, catalyzes cytosine deaminations (converting cytosines to uracils) as the initial DNA lesions that eventually lead to DSBs and CSR. Progress on AID structure integrates very well with knowledge about Ig class switch region nucleic acid structures that are supported by functional studies. It is an ideal time to review what is known about the mechanism of Ig CSR and its relation to somatic hypermutation. There have been many comprehensive reviews on various aspects of the CSR reaction and regulation of AID expression and activity. This review is focused on the relation between AID and switch region nucleic acid structures, with a particular emphasis on R-loops.

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哺乳动物免疫球蛋白类开关重组机制的研究进展
免疫球蛋白(Ig)类开关重组(CSR)是一种基因重排过程,通过B淋巴细胞改变Ig重链常数区,使Ig同型从IgM转换为IgG、IgA或IgE。在DNA水平上,CSR通过位于每个重链常数区上游的内含子开关区域的DNA双链断裂(dsb)的产生和连接发生。激活诱导脱氨酶(AID)是一种B细胞特异性酶,催化胞嘧啶脱氨(将胞嘧啶转化为尿嘧啶),作为最终导致dsb和CSR的初始DNA损伤。AID结构的进展与功能研究支持的Ig类开关区核酸结构的知识很好地结合在一起。现在是回顾Ig CSR机制及其与体细胞超突变关系的理想时机。关于CSR反应和AID表达和活性调控的各个方面已经有了很多全面的综述。本文综述了AID与开关区核酸结构的关系,重点介绍了r环。
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来源期刊
CiteScore
14.90
自引率
0.00%
发文量
6
期刊介绍: As the discipline of biochemistry and molecular biology have greatly advanced in the last quarter century, significant contributions have been made towards the advancement of general medicine, genetics, immunology, developmental biology, and biophysics. Investigators in a wide range of disciplines increasingly require an appreciation of the significance of current biochemical and molecular biology advances while, members of the biochemical and molecular biology community itself seek concise information on advances in areas remote from their own specialties. Critical Reviews in Biochemistry and Molecular Biology believes that well-written review articles prove an effective device for the integration and meaningful comprehension of vast, often contradictory, literature. Review articles also provide an opportunity for creative scholarship by synthesizing known facts, fruitful hypotheses, and new concepts. Accordingly, Critical Reviews in Biochemistry and Molecular Biology publishes high-quality reviews that organize, evaluate, and present the current status of high-impact, current issues in the area of biochemistry and molecular biology. Topics are selected on the advice of an advisory board of outstanding scientists, who also suggest authors of special competence. The topics chosen are sufficiently broad to interest a wide audience of readers, yet focused enough to be within the competence of a single author. Authors are chosen based on their activity in the field and their proven ability to produce a well-written publication.
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