Abstract
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.
Original language | English (US) |
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Pages (from-to) | 293-300 |
Number of pages | 8 |
Journal | Seminars in Immunology |
Volume | 24 |
Issue number | 4 |
DOIs | |
State | Published - Aug 2012 |
Keywords
- Activation-induced deaminase
- Antibody diversity
- Class switch recombination
- Cytosine deamination
- Double-strand breaks
- Epigenetic
- Mismatch repair
- Somatic hypermutation
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology