Apex2 is required for efficient somatic hypermutation but not for class switch recombination of immunoglobulin genes.
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.
Sabouri
Zahra
Z
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Kyoto, Japan.
Okazaki
Il-Mi
IM
Shinkura
Reiko
R
Begum
Nasim
N
Nagaoka
Hitoshi
H
Tsuchimoto
Daisuke
D
Nakabeppu
Yusaku
Y
Honjo
Tasuku
T
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004720:Endonucleases / Q000235:genetics / Q000502:physiology*; D005803:Genes, Immunoglobulin; D017578:Immunoglobulin Class Switching; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064251:Multifunctional Enzymes; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*
D064251:Multifunctional Enzymes; C476886:Apex2 protein, mouse; D004720:Endonucleases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase