The biochemistry of somatic hypermutation

Jonathan U. Peled, Li Kuang Fei, Maria D. Iglesias-Ussel, Sergio Roa, Susan L. Kalis, Myron F. Goodman, Matthew D. Scharff

Research output: Contribution to journalReview article

327 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)481-511
Number of pages31
JournalAnnual Review of Immunology
Volume26
DOIs
StatePublished - May 5 2008

Keywords

  • Activation-induced cytidine deaminase (AID, aicda)
  • Antibody diversity
  • Base excision repair
  • Error-prone repair
  • Germinal center
  • Mismatch repair

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Peled, J. U., Fei, L. K., Iglesias-Ussel, M. D., Roa, S., Kalis, S. L., Goodman, M. F., & Scharff, M. D. (2008). The biochemistry of somatic hypermutation. Annual Review of Immunology, 26, 481-511. https://doi.org/10.1146/annurev.immunol.26.021607.090236