Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota.
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.
Faili
Ahmad
A
INSERM U373, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730, Paris Cedex 15, France.
Aoufouchi
Said
S
Flatter
Eric
E
Guéranger
Quentin
Q
Reynaud
Claude-Agnès
CA
Weill
Jean-Claude
JC
D000915:Antibody Affinity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D003564:Cytidine Deaminase / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin; D014162:Transfection; D014407:Tumor Cells, Cultured; D000094769:DNA Polymerase iota; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D007136:Immunoglobulins; D012333:RNA, Messenger; D004259:DNA-Directed DNA Polymerase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D000094769:DNA Polymerase iota; C000722070:POLI protein, human