Somatic Hypermutation: The Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies. The Molecular Mechanisms Underlying the Production of Effective High-Affinity Antibodies.

Alberto Martin, Richard Chahwan, Jahan Yar Parsa, Matthew D. Scharff

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

V(D)J recombination produces a large repertoire of antibodies that can recognize diverse antigens. However, this repertoire is typically composed of antibodies that recognize their specific antigen with affinities that are too low to ensure the efficient clearance of infecting agents. To produce antibodies with higher affinity and sometimes changes in fine specificity, B-cells undergo a second antibody diversification process that in mice, humans, and many other species is called somatic hypermutation (SHM). Somatic hypermutation is initiated by and requires activation-induced cytidine deaminase, which converts pyrimidine (dC) to uridine (dU) on single-stranded DNA. The resulting dU:dG recruits noncanonical, error-prone forms of both base excision and mismatch repair to expand the process of SHM to include mutations in A:T as well as G:C base pairs. This ensemble of a highly mutagenic enzyme and subsequent error-prone repair results in the mutation of antibody V regions at about a million times higher frequency than occurs in other genes and is unique to antibody-forming B-cells.

Original languageEnglish (US)
Title of host publicationMolecular Biology of B Cells
Subtitle of host publicationSecond Edition
PublisherElsevier Inc.
Pages363-388
Number of pages26
ISBN (Electronic)9780123984906
ISBN (Print)9780123979339
DOIs
StatePublished - Dec 15 2014

Keywords

  • Activation-induced cytidine deaminase
  • Affinity maturation
  • Gene conversion
  • Mismatch repair
  • Msh2
  • Msh6
  • Polymerase η
  • Somatic hypermutation
  • Translesional error-prone polymerases
  • Uracil DNA glycosylase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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