AIDing antibody diversity by error-prone mismatch repair.
The creation of a highly diverse antibody repertoire requires the synergistic activity of a DNA mutator, known as activation-induced deaminase (AID), coupled with an error-prone repair process that recognizes the DNA mismatch catalyzed by AID. Instead of facilitating the canonical error-free response, which generally occurs throughout the genome, DNA mismatch repair (MMR) participates in an error-prone repair mode that promotes A:T mutagenesis and double-strand breaks at the immunoglobulin (Ig) genes. As such, MMR is capable of compounding the mutation frequency of AID activity as well as broadening the spectrum of base mutations; thereby increasing the efficiency of antibody maturation. We here review the current understanding of this MMR-mediated process and describe how the MMR signaling cascade downstream of AID diverges in a locus dependent manner and even within the Ig locus itself to differentially promote somatic hypermutation (SHM) and class switch recombination (CSR) in B cells.
Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Richard
R
Chahwan
Winfried
W
Edelmann
Matthew D
MD
Scharff
Sergio
S
Roa
D000818:Animals; D000916:Antibody Diversity; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D053843:DNA Mismatch Repair; D003641:Deamination; D006801:Humans; D009154:Mutation; D054875:Ubiquitination; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase