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

doi:10.1146/annurev.immunol.26.021607.090236

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

Cell Biology

Research output: Contribution to journal › Review article › peer-review

365 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 language	English (US)
Pages (from-to)	481-511
Number of pages	31
Journal	Annual Review of Immunology
Volume	26
DOIs	https://doi.org/10.1146/annurev.immunol.26.021607.090236
State	Published - 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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10.1146/annurev.immunol.26.021607.090236

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title = "The biochemistry of somatic hypermutation",

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.",

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AU - Peled, Jonathan U.

AU - Fei, Li Kuang

AU - Iglesias-Ussel, Maria D.

AU - Roa, Sergio

AU - Kalis, Susan L.

AU - Goodman, Myron F.

AU - Scharff, Matthew D.

PY - 2008

Y1 - 2008

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AB - 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.

KW - Activation-induced cytidine deaminase (AID, aicda)

KW - Antibody diversity

KW - Base excision repair

KW - Error-prone repair

KW - Germinal center

KW - Mismatch repair

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VL - 26

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JO - Annual Review of Immunology

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The biochemistry of somatic hypermutation

Abstract

Keywords

ASJC Scopus subject areas

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