Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation

J Exp Med. 2002 Feb 18;195(4):529-34. doi: 10.1084/jem.20012144.

Abstract

Somatic hypermutation (SHM) and class switch recombination (CSR) cause distinct genetic alterations at different regions of immunoglobulin genes in B lymphocytes: point mutations in variable regions and large deletions in S regions, respectively. Yet both depend on activation-induced deaminase (AID), the function of which in the two reactions has been an enigma. Here we report that B cell stimulation which induces CSR but not SHM, leads to AID-dependent accumulation of SHM-like point mutations in the switch mu region, uncoupled with CSR. These findings strongly suggest that AID itself or a single molecule generated by RNA editing function of AID may mediate a common step of SHM and CSR, which is likely to be involved in DNA cleavage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Base Sequence
  • Cytidine Deaminase / deficiency
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / metabolism*
  • Flow Cytometry
  • Gene Deletion
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin M / genetics*
  • Immunoglobulin Switch Region / genetics*
  • Mice
  • Molecular Sequence Data
  • Point Mutation / genetics
  • Polymerase Chain Reaction
  • RNA Editing
  • Recombination, Genetic / genetics*
  • Retroviridae / genetics
  • Somatic Hypermutation, Immunoglobulin / genetics*

Substances

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