title: High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells.
abstract: Ig gene somatic hypermutation in the germinal center (GC) B cells occurs at C and G at roughly the same frequency. In contrast, there is a 2-fold increase of mutations at A relative to T on the non-transcribed strand of the V genes but it is unclear what triggers such strand bias. Using an efficient mutagenesis system that recapitulates characteristic features of Ig gene hypermutation in the GC B cells, we found that low levels of AID induced similar frequency of mutations at A and T. However, high levels of AID specifically increased mutations at A, but not T, leading to strand bias. These results explain why strand bias of A:T mutations is observed only in the highly mutated V genes but not in the less mutated switch region or the BCL-6 gene. High levels of AID also increased the proportion of transversions at G relative to transversions at C. Our results identify a clue to the strand bias of A:T mutations and provide an in vitro model to elucidate this unsolved mystery in the hypermutation field.
authors: Laboratory for Immune Diversity, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama 230-0045, Japan.
authors: Chie
authors: C
authors: Kano
authors: Ji-Yang
authors: JY
authors: Wang
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D051560:Proto-Oncogene Proteins c-bcl-6; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase