The biochemistry of somatic hypermutation.
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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Related Subject Headings
- Somatic Hypermutation, Immunoglobulin
- Models, Genetic
- Immunology
- Immunoglobulin Variable Region
- Humans
- Germinal Center
- DNA Repair
- DNA Mismatch Repair
- Cytidine Deaminase
- Animals
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Start / End Page
Related Subject Headings
- Somatic Hypermutation, Immunoglobulin
- Models, Genetic
- Immunology
- Immunoglobulin Variable Region
- Humans
- Germinal Center
- DNA Repair
- DNA Mismatch Repair
- Cytidine Deaminase
- Animals