Differential programming of B cells in AID deficient mice

PLoS One. 2013 Jul 29;8(7):e69815. doi: 10.1371/journal.pone.0069815. Print 2013.

Abstract

The Aicda locus encodes the activation induced cytidine deaminase (AID) and is highly expressed in germinal center (GC) B cells to initiate somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin (Ig) genes. Besides these Ig specific activities in B cells, AID has been implicated in active DNA demethylation in non-B cell systems. We here determined a potential role of AID as an epigenetic eraser and transcriptional regulator in B cells. RNA-Seq on different B cell subsets revealed that Aicda(-/-) B cells are developmentally affected. However as shown by RNA-Seq, MethylCap-Seq, and SNP analysis these transcriptome alterations may not relate to AID, but alternatively to a CBA mouse strain derived region around the targeted Aicda locus. These unexpected confounding parameters provide alternative, AID-independent interpretations on genotype-phenotype correlations previously reported in numerous studies on AID using the Aicda(-/-) mouse strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / metabolism*
  • Cytidine Deaminase / deficiency*
  • Cytidine Deaminase / genetics
  • DNA Methylation / genetics
  • Genotype
  • Mice
  • Mice, Mutant Strains

Substances

  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase

Associated data

  • GEO/GSE47705

Grant support

MAH is supported by the Konigin Wilhemina Fonds (KWF) project NKI-2008-4112 to HJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.