AIDing antibody diversity by error-prone mismatch repair

Semin Immunol. 2012 Aug;24(4):293-300. doi: 10.1016/j.smim.2012.05.005. Epub 2012 Jun 14.


The creation of a highly diverse antibody repertoire requires the synergistic activity of a DNA mutator, known as activation-induced deaminase (AID), coupled with an error-prone repair process that recognizes the DNA mismatch catalyzed by AID. Instead of facilitating the canonical error-free response, which generally occurs throughout the genome, DNA mismatch repair (MMR) participates in an error-prone repair mode that promotes A:T mutagenesis and double-strand breaks at the immunoglobulin (Ig) genes. As such, MMR is capable of compounding the mutation frequency of AID activity as well as broadening the spectrum of base mutations; thereby increasing the efficiency of antibody maturation. We here review the current understanding of this MMR-mediated process and describe how the MMR signaling cascade downstream of AID diverges in a locus dependent manner and even within the Ig locus itself to differentially promote somatic hypermutation (SHM) and class switch recombination (CSR) in B cells.

Publication types

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

MeSH terms

  • Animals
  • Antibody Diversity*
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / immunology*
  • DNA Mismatch Repair*
  • Deamination
  • Humans
  • Mutation
  • Ubiquitination


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