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

Zahra Sabouri, Il mi Okazaki, Reiko Shinkura, Nasim A Begum, Hitoshi Nagaoka, Daisuke Tsuchimoto, Yusaku Nakabeppu, Tasuku Honjo

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29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)947-955
Number of pages9
JournalInternational Immunology
Volume21
Issue number8
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • DNA sequencing
  • Exonuclease activity
  • Flow cytometry
  • Gene targeting
  • RNAi

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