Antibody class switching occurs in mature B cells in response to antigen stimulation and costimulatory signals. It occurs by a unique type of intrachromosomal deletional recombination within special G-rich tandem repeated DNA sequences [called switch, or S, regions located upstream of each of the heavy chain constant (C(H)) region genes, except Cdelta]. The recombination is initiated by the B cell-specific activation-induced cytidine deaminase (AID), which deaminates cytosines in both the donor and acceptor S regions. AID activity converts several dC bases to dU bases in each S region, and the dU bases are then excised by the uracil DNA glycosylase UNG; the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). AID attacks both strands of transcriptionally active S regions, but how transcription promotes AID targeting is not entirely clear. Mismatch repair proteins are then involved in converting the resulting single-strand DNA breaks to double-strand breaks with DNA ends appropriate for end-joining recombination. Proteins required for the subsequent S-S recombination include DNA-PK, ATM, Mre11-Rad50-Nbs1, gammaH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are important for faithful joining of S regions, and in their absence aberrant recombination and chromosomal translocations involving S regions occur.

中文翻译：

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类开关重组的机制与调控。

抗体类别转换发生在成熟 B 细胞中，以响应抗原刺激和共刺激信号。它是由特殊类型的富含 G 的串联重复 DNA 序列 [称为开关或 S，位于每个重链恒定 (C(H)) 区基因上游的区域，Cdelta 除外] 内的一种独特类型的染色体内缺失重组而发生。重组由 B 细胞特异性激活诱导胞苷脱氨酶 (AID) 启动，该酶使供体和受体 S 区的胞嘧啶脱氨。AID 活性将每个 S 区的几个 dC 碱基转化为 dU 碱基，然后 dU 碱基被尿嘧啶 DNA 糖基化酶 UNG 切除；产生的无碱基位点被无嘌呤/无嘧啶核酸内切酶 (APE) 切开。AID 攻击具有转录活性的 S 区的两条链，但转录如何促进 AID 靶向并不完全清楚。然后，错配修复蛋白参与将产生的单链 DNA 断裂转化为双链断裂，DNA 末端适合末端连接重组。随后 SS 重组所需的蛋白质包括 DNA-PK、ATM、Mre11-Rad50-Nbs1、gammaH2AX、53BP1、Mdc1 和 XRCC4-连接酶 IV。这些蛋白质对于 S 区的忠实连接很重要，并且在它们不存在的情况下，会发生涉及 S 区的异常重组和染色体易位。Mdc1 和 XRCC4-连接酶 IV。这些蛋白质对于 S 区的忠实连接很重要，并且在它们不存在的情况下，会发生涉及 S 区的异常重组和染色体易位。Mdc1 和 XRCC4-连接酶 IV。这些蛋白质对于 S 区的忠实连接很重要，并且在它们不存在的情况下，会发生涉及 S 区的异常重组和染色体易位。