Abstract
Activation-induced cytidine deaminase (AID) is essential for class-switch recombination (CSR) and somatic hypermutation (SHM). Mutants with changes in the C-terminal region of AID retain SHM but lose CSR activity. Here we describe five mutants with alterations in the N-terminal region of AID that caused selective deficiency in SHM but retained CSR, suggesting that the CSR and SHM activities of AID may dissociate via interaction of CSR- or SHM-specific cofactors with different domains of AID. Unlike cells expressing C-terminal AID mutants, B cells expressing N-terminal AID mutants had mutations in the switch micro region, indicating that such mutations are generated by reactions involved in CSR but not SHM. Thus, we propose that separate domains of AID interact with specific cofactors to regulate these two distinct genetic events in a target-specific way.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Amino Acid Sequence
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cells, Cultured
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Cytidine Deaminase / chemistry*
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Cytidine Deaminase / deficiency
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Cytidine Deaminase / genetics
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Cytidine Deaminase / metabolism*
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Flow Cytometry
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Gene Expression Regulation
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Humans
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Immunoglobulin Class Switching / genetics*
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Immunoglobulin Class Switching / immunology*
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Mice
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Molecular Sequence Data
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Mutation / genetics
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NIH 3T3 Cells
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Nuclear Localization Signals / genetics
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Recombination, Genetic / genetics
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Recombination, Genetic / immunology
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Somatic Hypermutation, Immunoglobulin / genetics*
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Somatic Hypermutation, Immunoglobulin / immunology*
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
Substances
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Nuclear Localization Signals
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase