TY - JOUR
T1 - The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies
AU - Luo, Zhonghui
AU - Ronai, Diana
AU - Scharff, Matthew D.
N1 - Funding Information:
Supported by grants from the National Institutes of Health (CA 72649, CA 102705, and AI 43937). D. Ronai is supported by a Postdoctoral Fellowship from the Cancer Research Institute and a Harry Eagle Postdoctoral Award. M. D. Scharff is supported in part by the Harry Eagle Chair of the National Women's Division of the Albert Einstein College of Medicine.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
KW - Activation-induced cytidine deaminase
KW - class-switch recombination
KW - immunodeficiency
KW - lymphoma
KW - somatic hypermutation
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U2 - 10.1016/j.jaci.2004.07.049
DO - 10.1016/j.jaci.2004.07.049
M3 - Review article
C2 - 15480307
AN - SCOPUS:4944257670
SN - 0091-6749
VL - 114
SP - 726
EP - 735
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 4
ER -