Activation-induced cytidine deaminase initiates immunoglobulin gene conversion and hypermutation by a common intermediate

PLoS Biol. 2004 Jul;2(7):E179. doi: 10.1371/journal.pbio.0020179. Epub 2004 Jul 13.

Abstract

Depending on the species and the lymphoid organ, activation-induced cytidine deaminase (AID) expression triggers diversification of the rearranged immunoglobulin (Ig) genes by pseudo V (psiV) gene- templated gene conversion or somatic hypermutation. To investigate how AID can alternatively induce recombination or hypermutation, psiV gene deletions were introduced into the rearranged light chain locus of the DT40 B-cell line. We show that the stepwise removal of the psiV donors not only reduces and eventually abolishes Ig gene conversion, but also activates AID-dependent Ig hypermutation. This strongly supports a model in which AID induces a common modification in the rearranged V(D)J segment, leading to a conversion tract in the presence of nearby donor sequences and to a point mutation in their absence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chickens
  • Cloning, Molecular
  • Cytidine Deaminase / genetics*
  • DNA Mutational Analysis
  • Gene Conversion*
  • Gene Deletion
  • Immunoglobulins / genetics*
  • Models, Genetic
  • Molecular Sequence Data
  • Mutagenesis
  • Mutation*
  • Point Mutation
  • Polymerase Chain Reaction
  • Recombination, Genetic
  • VDJ Recombinases / metabolism

Substances

  • Immunoglobulins
  • VDJ Recombinases
  • Cytidine Deaminase

Associated data

  • GENBANK/GGU92461
  • GENBANK/U01047
  • GENBANK/X92865
  • RefSeq/NM_009645
  • RefSeq/NM_020661
  • RefSeq/NM_204157