IgH chain class switch recombination: mechanism and regulation.

IgH chain class switch recombination: mechanism and regulation.
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DOI:
10.4049/jimmunol.1401849
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发表时间:
2014-12-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Schrader CE
Schrader CE
中科院分区:
其他
文献类型:
--
作者:
Stavnezer J;Schrader CE

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免疫球蛋白重链类转换在成熟的幼稚B细胞激活后迅速发生,导致从表达IgM和IgD转换到表达免疫球蛋白、IgE或IgA;这种转换提高了抗体清除诱导体液免疫反应的病原体的能力。类转换是通过两个不同的开关区(S)之间的缺失重组而发生的,每个开关区都与一个重链恒定(CH)区基因相关。类开关重组(CSR)是由激活诱导的胞苷脱氨酶(AID)启动的,它将S区域的胞苷转化为尿嘧啶。尿嘧啶随后被两条DNA修复途径移除,导致突变、单链DNA断裂和CSR所需的双链断裂。我们讨论了CSR的几个方面,包括CSR是如何诱导的,CSR在B细胞祖细胞中的作用,转录和染色体环在CSR中的作用,以及某些DNA修复酶在CSR中的作用。
Ig heavy chain class switching occurs rapidly after activation of mature naïve B cells, resulting in a switch from expressing IgM and IgD to expression of IgG, IgE, or IgA; this switch improves the ability of antibodies to remove the pathogen that induces the humoral immune response. Class switching occurs by a deletional recombination between two different switch (S) regions, each of which is associated with a heavy chain constant (CH) region gene. Class switch recombination (CSR) is instigated by activation-induced cytidine deaminase (AID), which converts cytosines in S 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 for transcription and chromosomal looping in CSR, and the roles of certain DNA repair enzymes in CSR.
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