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J Immunol. 2010 Jun 1;184(11):6177-87. doi: 10.4049/jimmunol.0904085. Epub 2010 May 5.

p53 represses class switch recombination to IgG2a through its antioxidant function.

Author information

  • 1Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.

Erratum in

  • J Immunol. 2011 Nov 1;187(9):4920.

Abstract

Ig class switch recombination (CSR) occurs in activated mature B cells, and causes an exchange of the IgM isotype for IgG, IgE, or IgA isotypes, which increases the effectiveness of the humoral immune response. DNA ds breaks in recombining switch (S) regions, where CSR occurs, are required for recombination. Activation-induced cytidine deaminase initiates DNA ds break formation by deamination of cytosines in S regions. This reaction requires reactive oxygen species (ROS) intermediates, such as hydroxyl radicals. In this study we show that the ROS scavenger N-acetylcysteine inhibits CSR. We also demonstrate that IFN-gamma treatment, which is used to induce IgG2a switching, increases intracellular ROS levels, and activates p53 in switching B cells, and show that p53 inhibits IgG2a class switching through its antioxidant-regulating function. Finally, we show that p53 inhibits DNA breaks and mutations in S regions in B cells undergoing CSR, suggesting that p53 inhibits the activity of activation-induced cytidine deaminase.

PMID:
20483782
[PubMed - indexed for MEDLINE]
PMCID:
PMC3235438
Free PMC Article

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