The biochemistry of somatic hypermutation

Annu Rev Immunol. 2008;26:481-511. doi: 10.1146/annurev.immunol.26.021607.090236.

Abstract

Affinity maturation of the humoral response is mediated by somatic hypermutation of the immunoglobulin (Ig) genes and selection of higher-affinity B cell clones. Activation-induced cytidine deaminase (AID) is the first of a complex series of proteins that introduce these point mutations into variable regions of the Ig genes. AID deaminates deoxycytidine residues in single-stranded DNA to deoxyuridines, which are then processed by DNA replication, base excision repair (BER), or mismatch repair (MMR). In germinal center B cells, MMR, BER, and other factors are diverted from their normal roles in preserving genomic integrity to increase diversity within the Ig locus. Both AID and these components of an emerging error-prone mutasome are regulated on many levels by complex mechanisms that are only beginning to be elucidated.

Publication types

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

MeSH terms

  • Animals
  • Cytidine Deaminase / metabolism
  • DNA Mismatch Repair
  • DNA Repair*
  • Germinal Center / immunology
  • Germinal Center / metabolism
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Models, Genetic
  • Somatic Hypermutation, Immunoglobulin*

Substances

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