Department of Microbiology & Molecular Genetics, Biomedical Physical Sciences, Michigan State University, East Lansing, MI, USA.
Department of Pathology, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Crit Rev Biochem Mol Biol. 2019 Aug;54(4):333-351. doi: 10.1080/10409238.2019.1659227. Epub 2019 Sep 11.
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.
免疫球蛋白(Ig)类别转换重组(CSR)是 B 淋巴细胞改变 Ig 重链恒定区的基因重排过程,从而允许 Ig 同种型从 IgM 转换为 IgG、IgA 或 IgE。在 DNA 水平上,CSR 通过在每个重链恒定区上游的内含子开关区生成和连接 DNA 双链断裂(DSB)来发生。激活诱导的脱氨酶(AID)是一种 B 细胞特异性酶,可催化胞嘧啶脱氨酶(将胞嘧啶转化为尿嘧啶)作为最初的 DNA 损伤,最终导致 DSB 和 CSR。AID 结构的研究进展与支持功能研究的 Ig 类别转换区核酸结构的知识非常吻合。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。已经有许多关于 CSR 反应和 AID 表达和活性调节的各个方面的综合评论。本综述重点关注 AID 与开关区核酸结构的关系,特别强调 R 环。
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