The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies.

J Allergy Clin Immunol 2004 Oct;114(4):726-35; quiz 736

Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Before exposure to antigen, antibodies with a wide diversity of antigen-binding sites are created by V(D)J rearrangement. After exposure to antigen, further diversification is accomplished by means of somatic hypermutation of the antibody variable region genes and class-switch recombination between the heavy-chain mu constant region and the downstream gamma, epsilon, and alpha constant region. The variable region mutations are responsible for the affinity maturation of the antibody response, whereas class-switch recombination enables the antibodies to be distributed throughout the body and to carry out different effector functions. Both somatic mutation and class switching require an enzyme called activation-induced cytidine deaminase (AID) that converts deoxycytidines to deoxyuracils on single-stranded DNA. Genetic defects of AID in human subjects result in hyper-IgM syndrome type 2. The analysis of both mutant mice and immunodeficient patients has led to a better understanding of the mechanism of action and role of AID in immunity, as well as in the malignant transformation of B cells.

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http://dx.doi.org/10.1016/j.jaci.2004.07.049DOI Listing
October 2004
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