Journal
IMMUNOLOGIC RESEARCH
Volume 55, Issue 1-3, Pages 287-297Publisher
HUMANA PRESS INC
DOI: 10.1007/s12026-012-8369-4
Keywords
Class switch recombination; Somatic hypermutation; Switch region; Variable region; Activation; induced deaminase
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Funding
- University of Colorado School of Medicine
- Leukemia Research Foundation
- Boettcher Foundation
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More than a decade ago, activation-induced deaminase (AID) was identified as the initiator for somatic hypermutation (SHM) and class switch recombination (CSR). Since then, tremendous progress has been achieved toward elucidating how AID functions. AID targets the highly repetitive switch regions of the immunoglobulin heavy chain (IgH) locus to induce DNA double-strand breaks (DSBs), which can be rejoined, leading to switch of constant regions of antibody. When targeting to variable region exons of IgH and IgL loci, AID predominantly induces point mutations, termed SHM, resulting in increased affinity of antibody for antigen. While SHM and CSR enhance antibody diversity, AID-initiated DSBs and mutations may predispose B cells to carcinogenesis. This review focuses on the mechanisms that provide the specificity of AID targeting to Ig loci and the role of AID in genomic instability.
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