TY - JOUR
T1 - Cutting edge
T2 - The G-U mismatch glycosylase methyl-CpG binding domain 4 is dispensable for somatic hypermutation and class switch recombination
AU - Bardwell, Philip D.
AU - Martin, Alberto
AU - Wong, Edmund
AU - Li, Ziqiang
AU - Edelmann, Winfried
AU - Scharff, Matthew D.
PY - 2003/2/15
Y1 - 2003/2/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.170.4.1620
DO - 10.4049/jimmunol.170.4.1620
M3 - Article
C2 - 12574322
AN - SCOPUS:0037442190
SN - 0022-1767
VL - 170
SP - 1620
EP - 1624
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -