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 journalArticle

311 Citations (Scopus)

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 - 2008

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Biochemistry
Immunoglobulin Genes
DNA Mismatch Repair
DNA Repair
B-Lymphocytes
Deoxyuridine
Deoxycytidine
Germinal Center
Single-Stranded DNA
DNA Replication
Point Mutation
Immunoglobulins
Clone Cells
AICDA (activation-induced cytidine deaminase)
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology

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

The biochemistry of somatic hypermutation. / Peled, Jonathan U.; Fei, Li Kuang; Iglesias-Ussel, Maria D.; Roa, Sergio; Kalis, Susan L.; Goodman, Myron F.; Scharff, Matthew D.

In: Annual Review of Immunology, Vol. 26, 2008, p. 481-511.

Research output: Contribution to journalArticle

Peled, JU, Fei, LK, Iglesias-Ussel, MD, Roa, S, Kalis, SL, Goodman, MF & Scharff, MD 2008, 'The biochemistry of somatic hypermutation', Annual Review of Immunology, vol. 26, pp. 481-511. https://doi.org/10.1146/annurev.immunol.26.021607.090236
Peled JU, Fei LK, Iglesias-Ussel MD, Roa S, Kalis SL, Goodman MF et al. The biochemistry of somatic hypermutation. Annual Review of Immunology. 2008;26:481-511. https://doi.org/10.1146/annurev.immunol.26.021607.090236
Peled, Jonathan U. ; Fei, Li Kuang ; Iglesias-Ussel, Maria D. ; Roa, Sergio ; Kalis, Susan L. ; Goodman, Myron F. ; Scharff, Matthew D. / The biochemistry of somatic hypermutation. In: Annual Review of Immunology. 2008 ; Vol. 26. pp. 481-511.
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