Cutting edge

The G-U mismatch glycosylase methyl-CpG binding domain 4 is dispensable for somatic hypermutation and class switch recombination

Philip D. Bardwell, Alberto Martin, Edmund Wong, Ziqiang Li, Winfried Edelmann, Matthew D. Scharff

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1620-1624
Number of pages5
JournalJournal of Immunology
Volume170
Issue number4
StatePublished - Feb 15 2003

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Genetic Recombination
Immunoglobulin Genes
Uracil-DNA Glycosidase
Cytidine
Peyer's Patches
Deamination
Methyl CpG Binding Domain
Immunization
B-Lymphocytes
AICDA (activation-induced cytidine deaminase)

ASJC Scopus subject areas

  • Immunology

Cite this

Cutting edge : The G-U mismatch glycosylase methyl-CpG binding domain 4 is dispensable for somatic hypermutation and class switch recombination. / Bardwell, Philip D.; Martin, Alberto; Wong, Edmund; Li, Ziqiang; Edelmann, Winfried; Scharff, Matthew D.

In: Journal of Immunology, Vol. 170, No. 4, 15.02.2003, p. 1620-1624.

Research output: Contribution to journalArticle

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