Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes
Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes
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DOI：
10.1093/intimm/dxp061
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Honjo, Tasuku
中科院分区：
文献类型：
--
作者：
Sabouri, Zahra;Okazaki, Il-mi;Honjo, Tasuku
在Ig基因的类开关重组(CSR)和体细胞超突变(SHM)中，DNA裂解步骤都是由激活诱导的胞苷脱氨酶(AID)启动的。然而，SHM和CSR中DNA链断裂的详细机制在很大程度上仍不清楚。最近，无嘌呤/脱嘧啶核酸内切酶Apex1和Apex2被报道参与了CSR的DNA切割步骤。在这里，我们使用Apex2缺陷小鼠检测了Apex2在SHM中的作用，发现Apex2缺陷导致SHM频率和每个突变克隆的突变数量急剧减少，而不影响碱基替换模式。这些结果表明，Apex2可能通过其3‘-5’外切酶活性在SHM中发挥关键作用。出乎意料的是，在Apex2缺陷的B细胞中，CSR的效率并没有降低。此外，在CH12F3-2B淋巴瘤细胞中，Apex1基因敲除并不影响CSR频率，这表明Apex1和Apex2在CSR中都不起主要作用。
The DNA cleavage step in both the class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes is initiated by activation-induced cytidine deaminase (AID). However, the detailed mechanisms of the DNA strand cleavage in SHM and CSR are still largely unknown. Recently, the apurinic/apyrimidinic endonucleases, Apex1 and Apex2, were reported to be involved in the DNA cleavage step of CSR. Here, we examined the role of Apex2 in SHM using Apex2-deficient mice and found that the Apex2 deficiency caused a drastic reduction in the frequency of SHM and the number of mutations per mutated clone without affecting the pattern of base substitution. These results suggest that Apex2 may play a critical role in SHM through its 3'-5' exonuclease activity. Unexpectedly, the efficiency of CSR was not reduced in Apex2-deficient B cells. In addition, Apex1 knockdown in CH12F3-2 B lymphoma cells did not affect the CSR frequency, suggesting that neither Apex1 nor Apex2 plays a major role in CSR.