Abstract
Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed Vh/Vl genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an error-prone DNA synthesis step that introduces the mutations. The Y family of DNA polymerases--pol eta, pol iota, pol kappa and rev1--are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template. By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibody Affinity / genetics
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B-Lymphocytes / immunology
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Blotting, Western
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Burkitt Lymphoma / enzymology
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Burkitt Lymphoma / genetics
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Burkitt Lymphoma / immunology
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Cytidine Deaminase / metabolism
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DNA Polymerase iota
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DNA-Directed DNA Polymerase / deficiency
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DNA-Directed DNA Polymerase / genetics
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DNA-Directed DNA Polymerase / metabolism*
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Gene Deletion
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Genes, Immunoglobulin / genetics*
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Humans
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Immunoglobulins / genetics
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Immunoglobulins / immunology
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Molecular Sequence Data
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Mutation / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Somatic Hypermutation, Immunoglobulin*
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Transfection
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Tumor Cells, Cultured
Substances
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Immunoglobulins
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RNA, Messenger
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DNA-Directed DNA Polymerase
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase
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DNA Polymerase iota
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POLI protein, human