International Immunology Advance Access originally published online on June 25, 2009
International Immunology 2009 21(8):947-955; doi:10.1093/intimm/dxp061
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Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes
1 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
2 Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
3 Present address: Division of Immune Regulation, Institute for Genome Research, University of Tokushima, Tokushima, Japan
Correspondence to: T. Honjo; E-mail: honjo{at}mfour.med.kyoto-u.ac.jp
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.
Keywords: DNA sequencing, exonuclease activity, flow cytometry, gene targeting, RNAi
* These authors contributed equally to this study.
Transmitting editor: S. Koyasu
Received 22 April 2009, accepted 29 May 2009.