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

Zhonghui Luo, Diana Ronai, Matthew D. Scharff

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)726-736
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Volume114
Issue number4
DOIs
StatePublished - Oct 2004

Fingerprint

B-Lymphocytes
Antigens
Genetic Recombination
Antibodies
Hyper-IgM Immunodeficiency Syndrome
Switch Genes
Immunoglobulin Class Switching
Neoplasms
Deoxycytidine
Mutation
Enzyme Activation
Single-Stranded DNA
Antibody Formation
Immunity
Binding Sites
AICDA (activation-induced cytidine deaminase)

Keywords

  • Activation-induced cytidine deaminase
  • class-switch recombination
  • immunodeficiency
  • lymphoma
  • somatic hypermutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The role of activation-induced cytidine deaminase in antibody diversification, immunodeficiency, and B-cell malignancies. / Luo, Zhonghui; Ronai, Diana; Scharff, Matthew D.

In: Journal of Allergy and Clinical Immunology, Vol. 114, No. 4, 10.2004, p. 726-736.

Research output: Contribution to journalArticle

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