| First Author | Green B | Year | 2011 |
| Journal | Blood | Volume | 118 |
| Issue | 11 | Pages | 3013-8 |
| PubMed ID | 21788338 | Mgi Jnum | J:177080 |
| Mgi Id | MGI:5293582 | Doi | 10.1182/blood-2011-03-345991 |
| Citation | Green B, et al. (2011) The mismatch repair pathway functions normally at a non-AID target in germinal center B cells. Blood 118(11):3013-8 |
| abstractText | Deficiency in Msh2, a component of the mismatch repair (MMR) system, leads to an approximately 10-fold increase in the mutation frequency in most tissues. By contrast, Msh2 deficiency in germinal center (GC) B cells decreases the mutation frequency at the IgH V region as a dU:dG mismatch produced by AID initiates modifications by MMR, resulting in mutations at nearby A:T base pairs. This raises the possibility that GC B cells express a factor that converts MMR into a globally mutagenic pathway. To test this notion, we investigated whether MMR corrects mutations in GC B cells at a gene that is not mutated by AID. Strikingly, we found that GC B cells accumulate 5 times more mutations at a reporter gene than during the development of the mouse. Notably, the mutation frequency at this reporter gene was approximately 10 times greater in Msh2(-/-) compared with wild-type GC B cells cells. In contrast to the V region, the increased level of mutations at A:T base pairs in GC B cells was not caused by MMR. These results show that in GC B cells, (1) MMR functions normally at an AID-insensitive gene and (2) the frequency of background mutagenesis is greater in GC B cells than in their precursor follicular B cells. |
