| First Author | Winter DB | Year | 2003 |
| Journal | J Immunol | Volume | 170 |
| Issue | 11 | Pages | 5558-62 |
| PubMed ID | 12759433 | Mgi Jnum | J:83465 |
| Mgi Id | MGI:2662058 | Doi | 10.4049/jimmunol.170.11.5558 |
| Citation | Winter DB, et al. (2003) Normal somatic hypermutation of Ig genes in the absence of 8-hydroxyguanine-DNA glycosylase. J Immunol 170(11):5558-62 |
| abstractText | 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 kappa 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. |
