AIDing antibody diversity by error-prone mismatch repair

Richard Chahwan, Winfried Edelmann, Matthew D. Scharff, Sergio Roa

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)293-300
Number of pages8
JournalSeminars in Immunology
Volume24
Issue number4
DOIs
StatePublished - Aug 2012

Fingerprint

Antibody Diversity
DNA Mismatch Repair
Immunoglobulin Genes
Antibodies
DNA
Mutation Rate
Mutagenesis
Genetic Recombination
Immunoglobulins
B-Lymphocytes
Genome
Mutation
AICDA (activation-induced cytidine deaminase)

Keywords

  • Activation-induced deaminase
  • Antibody diversity
  • Class switch recombination
  • Cytosine deamination
  • Double-strand breaks
  • Epigenetic
  • Mismatch repair
  • Somatic hypermutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

AIDing antibody diversity by error-prone mismatch repair. / Chahwan, Richard; Edelmann, Winfried; Scharff, Matthew D.; Roa, Sergio.

In: Seminars in Immunology, Vol. 24, No. 4, 08.2012, p. 293-300.

Research output: Contribution to journalArticle

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