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

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

Research output: Contribution to journalArticle

25 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 - Oct 2 2009

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Immunoglobulin Genes
Genetic Recombination
DNA Cleavage
DNA-(Apurinic or Apyrimidinic Site) Lyase
Exonucleases
B-Cell Lymphoma
B-Lymphocytes
Clone Cells
Mutation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes. / Sabouri, Zahra; Okazaki, Il Mi; Shinkura, Reiko; Begum, Nasim; Nagaoka, Hitoshi; Tsuchimoto, Daisuke; Nakabeppu, Yusaku; Honjo, Tasuku.

In: International Immunology, Vol. 21, No. 8, 02.10.2009, p. 947-955.

Research output: Contribution to journalArticle

Sabouri, Zahra ; Okazaki, Il Mi ; Shinkura, Reiko ; Begum, Nasim ; Nagaoka, Hitoshi ; Tsuchimoto, Daisuke ; Nakabeppu, Yusaku ; Honjo, Tasuku. / Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes. In: International Immunology. 2009 ; Vol. 21, No. 8. pp. 947-955.
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