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

• Published in: Journal of allergy and clinical immunology Vol. 114; no. 4; pp. 726 - 735
• Main Authors: Luo, Zhonghui, Ronai, Diana, Scharff, Matthew D.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.10.2004; Elsevier; Elsevier Limited
• Subjects: Activation-induced cytidine deaminase; Antibody Diversity - immunology; Binding sites; Biological and medical sciences; class-switch recombination; Cytidine Deaminase; Cytosine Deaminase - immunology; Deoxyribonucleic acid; Diversification; DNA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Human subjects; Humans; Immune system; immunodeficiency; Immunoglobulin Class Switching - immunology; Immunologic Deficiency Syndromes - immunology; Immunopathology; Leukemia, B-Cell - immunology; lymphoma; Lymphoma, B-Cell - immunology; Medical sciences; Mutation; Plasmacytoma - immunology; somatic hypermutation; Somatic Hypermutation, Immunoglobulin - immunology; DLBCL; CSR; lymphoma; Activation-induced cytidine deaminase; AP endonuclease; GLT; UNG; dU; DSB; somatic hypermutation; HIGM2; MMR; APOBEC-1; NLS; SHM; immunodeficiency; NHEJ; AID; GC; ssDNA; class-switch recombination; dC; SR; Immunopathology; Recombination; Enzyme; Antibody; Malignant hemopathy; B-Lymphocyte; Malignant tumor; Diversification; Immune deficiency; Lymphoma; Immunology; Lymphoproliferative syndrome; Hydrolases; Isotype switching; Cytidine deaminase
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.07.049

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 μ constant region and the downstream γ, ε, and α 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.