The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies.
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.
Luo
Zhonghui
Z
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ronai
Diana
D
Scharff
Matthew D
MD
D000916:Antibody Diversity / Q000276:immunology*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D015448:Leukemia, B-Cell / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology*; D010954:Plasmacytoma / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase