Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes

作者：Sabouri Zahra; Okazaki Il mi; Shinkura Reiko; Begum Nasim; Nagaoka Hitoshi; Tsuchimoto Daisuke; Nakabeppu Yusaku; Honjo Tasuku^*

来源：International Immunology, 2009, 21(8): 947-955.

DOI：10.1093/intimm/dxp061

• DNA sequencing
• exonuclease activity
• flow cytometry
• gene targeting
• RNAi

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.

• 出版日期2009-8