Normal somatic hypermutation of Ig genes in the absence of 8-hydroxyguanine-DNA glycosylase

David B. Winter, Quy H. Phung, Xianmin Zeng, Erling Seeberg, Deborah E. Barnes, Tomas Lindahl, Patricia J. Gearhart

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The hypermutation cascade in Ig V genes can be initiated by deamination of cytosine in DNA to uracil by activation-induced cytosine deaminase and its removal by uracil-DNA glycosylase. To determine whether damage to guanine also contributes to hypermutation, we examined the glycosylase that removes oxidized guanine from DNA, 8-hydroxyguanine-DNA glycosylase (OGG1). OGG1 has been reported to be overexpressed in human B cells from germinal centers, where mutation occurs, and could be involved in initiating Ab diversity by removing modified guanines. In this study, mice deficient in Ogg1 were immunized, and V genes from the H and κ L chain loci were sequenced. Both the frequency of mutation and the spectra of nucleotide substitutions were similar in ogg1-/- and Ogg1+/+ clones. More importantly, there was no significant increase in G:C to T:A transversions in the ogg1-/- clones, which would be expected if 8-hydroxyguanine remained in the DNA. Furthermore, Ogg1 was not up-regulated in murine B cells from germinal centers. These findings show that hypermutation is unaffected in the absence of Ogg1 activity and indicate that 8-hydroxyguanine lesions most likely do not cause V gene mutations.

Original languageEnglish (US)
Pages (from-to)5558-5562
Number of pages5
JournalJournal of Immunology
Issue number11
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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