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.
Peled
Jonathan U
JU
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. jpeled@aecom.yu.edu
Kuang
Fei Li
FL
Iglesias-Ussel
Maria D
MD
Roa
Sergio
S
Kalis
Susan L
SL
Goodman
Myron F
MF
Scharff
Matthew D
MD
D000818:Animals; D003564:Cytidine Deaminase / Q000378:metabolism; D053843:DNA Mismatch Repair; D004260:DNA Repair; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008957:Models, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007135:Immunoglobulin Variable Region; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase