| First Author | Bardwell PD | Year | 2003 |
| Journal | J Immunol | Volume | 170 |
| Issue | 4 | Pages | 1620-4 |
| PubMed ID | 12574322 | Mgi Jnum | J:82295 |
| Mgi Id | MGI:2652008 | Doi | 10.4049/jimmunol.170.4.1620 |
| Citation | Bardwell PD, et al. (2003) Cutting edge: the G-U mismatch glycosylase methyl-CpG binding domain 4 is dispensable for somatic hypermutation and class switch recombination. J Immunol 170(4):1620-4 |
| abstractText | Affinity maturation of the humoral response is accomplished by somatic hypermutation and class switch recombination (CSR) of Ig genes. Activation-induced cytidine deaminase likely initiates these processes by deamination of cytidines in the V and switch regions of Ig genes. This activity is expected to produce G-U mismatches that can be substrates for MutS homolog 2/MutS homolog 6 heterodimers and for uracil DNA glycosylase. However, G-T and G-U mismatches are also substrates of the methyl-CpG binding domain 4 (Mbd4) glycosylase. To determine whether Mbd4 functions downstream of activation-induced cytidine deaminase activity, we examined somatic hypermutation and CSR in Mbd4(-/-) mice. In this study, we report that CSR, as analyzed by an in vitro switch assay and by in vivo immunizations, is unaffected in Mbd4(-/-) mice. In addition, the hypermutated JH2 to JH4 region in Peyer's patch B cells showed no effects as a result of Mbd4 deficiency. These data indicate that the Mbd4 glycosylase does not significantly contribute to mechanisms of Ab diversification. |
