A Comprehensive Analysis of the Effects of the Deaminase AID on the Transcriptome and Methylome of Activated B Cells

Nat Immunol. 2013 Jul;14(7):749-55. doi: 10.1038/ni.2616. Epub 2013 May 26.

Abstract

Beyond its well-characterized functions in antibody diversification, the cytidine deaminase AID can catalyze off-target DNA damage and has been hypothesized to edit RNA and mediate DNA demethylation. To comprehensively examine the effects of AID on the transcriptome and the pattern of DNA methylation ('methylome'), we analyzed AID-deficient (Aicda(-/-)), wild-type and AID-overexpressing activated B cells by high-throughput RNA sequencing (RNA-Seq) and reduced-representation bisulfite sequencing (RRBS). These analyses confirmed the known role of AID in immunoglobulin isotype switching and also demonstrated few other effects of AID on gene expression. Additionally, we detected no evidence of AID-dependent editing of mRNA or microRNA. Finally, the RRBS data did not support the proposed role for AID in regulating DNA methylation. Thus, despite evidence of its additional activities in other systems, antibody diversification seems to be the sole physiological function of AID in activated B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Cytidine Deaminase / immunology*
  • Female
  • Immunoglobulin Isotypes / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / chemistry
  • MicroRNAs / genetics
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Sequence Analysis, DNA
  • Somatic Hypermutation, Immunoglobulin / immunology*
  • Transcriptome / immunology*

Substances

  • Immunoglobulin Isotypes
  • MicroRNAs
  • RNA, Messenger
  • Cytidine Deaminase