Activation-induced cytidine deaminase: structure-function relationship as based on the study of mutants.
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TL;DR: Together, these data strongly suggest that AID, a master molecule for antibody diversification, exerts its activity on CSR not only as a cytidine deaminase enzyme but also as a docking protein, recruiting specific cofactors to a multimeric complex.
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Abstract: Activation-induced cytidine deaminase (AID; gene symbol AICDA) is the key molecule required to induce immunoglobulin (Ig) class switch recombination (CSR) and somatic hypermutation (SHM) of the variable regions of Ig genes. Its deficiency causes a form of hyper-IgM (HIGM) syndrome. The study of natural AID mutants associated with HIGM as well as engineered mutants led to the characterization of the active domains of the protein. AID, through its cytidine deaminase activity, induces a targeted DNA lesion as an early step required for both CSR and SHM. Besides its cytidine deaminase activity, AID plays a further essential role in CSR, likely by recruiting CSR-specific cofactors by its C-terminus. A similar binding of SHM-specific cofactors to the N-terminal part is suggested by the functional characteristics of N(ter) AID artificial mutants. These data require confirmation in vivo. Finally, AID acts as a homo-, di-, or multimeric complex. Together, these data strongly suggest that AID, a master molecule for antibody diversification, exerts its activity on CSR not only as a cytidine deaminase enzyme but also as a docking protein, recruiting specific cofactors to a multimeric complex.
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Citations
AID Recognizes Structured DNA for Class Switch Recombination
Qi Qiao,Li Wang,Li Wang,Fei-Long Meng,Joyce K. Hwang,Joyce K. Hwang,Joyce K. Hwang,Frederick W. Alt,Frederick W. Alt,Frederick W. Alt,Hao Wu,Hao Wu +11 more
TL;DR: The data implicate intrinsic preference of AIDs for structured substrates and uncover the importance of G4 recognition and oligomerization of AID in CSR.
164
Primary B-cell immunodeficiencies.
TL;DR: B-cell specific immune defects categorized by presence or absence of peripheral B-cells, immunoglobulins isotypes and evidence of antibody impairment are described.
66
An Evolutionary View of the Mechanism for Immune and Genome Diversity
TL;DR: In this article, an ortholog of activation-induced cytidine deaminase (AID) was, evolutionarily, the first enzyme to generate acquired immune diversity by catalyzing gene conversion and probably somatic hypermutation (SHM).
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Patent
Methods of generating libraries and uses thereof
Peter Bowers,Andrew B. Cubitt,Robert A. Horlick +2 more
- 20 Feb 2008
TL;DR: In this paper, a method for the generation of humanized antibody heavy chain protein and light chain protein using Activation Induced Cytidine Deaminase (AID) was proposed.
55
Immunoglobulin class switch recombination deficiencies.
TL;DR: In Inherited defects in class switch recombination variably associated to defects in somatic hypermutation are a group of genetically heterogeneous diseases, the characterization of which has allowed recognition that T-B cell interaction (resulting in CD40-mediated signaling), intrinsic B cell mechanisms, and complex DNA repair machinery are involved in classswitch recombination and somatichypermutation.
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References
Class Switch Recombination and Hypermutation Require Activation-Induced Cytidine Deaminase (AID), a Potential RNA Editing Enzyme
Masamichi Muramatsu,Kazuo Kinoshita,Sidonia Fagarasan,Shuichi Yamada,Yoichi Shinkai,Tasuku Honjo +5 more
TL;DR: Results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation in CH12F3-2 B lymphoma.
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Clonal selection and learning in the antibody system
TL;DR: A second selection process occurs during immune responses in which a new antibody repertoire is generated through somatic hypermutation, where only mutants binding antigen with high affinity survive to become memory cells.
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Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2).
Patrick Revy,Taro Muto,Yves Levy,Frederic Geissmann,Alessandro Plebani,Ozden Sanal,Nadia Catalan,Monique Forveille,Dufourcq-Lagelouse R,Andrew R. Gennery,Ilhan Tezcan,Fügen Ersoy,Hülya Kayserili,Alberto G. Ugazio,Nicole Brousse,Masamichi Muramatsu,Luigi D. Notarangelo,Kazuo Kinoshita,Tasuku Honjo,Alain Fischer,Anne Durandy +20 more
TL;DR: The phenotype observed in HIGM2 patients (and in AID-/- mice) demonstrates the absolute requirement for AID in several crucial steps of B cell terminal differentiation necessary for efficient antibody responses.
1.6K
Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells
TL;DR: It is reported here that human IgM+IgD+ peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM-only tonsillar germinal center and plasma cells, which may represent a general marker for memory B cells in humans.
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Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells.
Masamichi Muramatsu,V.S. Sankaranand,Shrikant Anant,Manabu Sugai,Kazuo Kinoshita,Nicholas O. Davidson,Tasuku Honjo +6 more
TL;DR: Findings suggest that AID is a new member of the RNA-editing deaminase family and may play a role in genetic events in the germinal center B cell.
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