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High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells.
- Source :
-
Molecular immunology [Mol Immunol] 2013 Jul; Vol. 54 (3-4), pp. 397-402. Date of Electronic Publication: 2013 Feb 09. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- B-Lymphocytes metabolism
B-Lymphocytes physiology
Base Sequence
Burkitt Lymphoma enzymology
Burkitt Lymphoma immunology
Cell Line
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Germinal Center metabolism
Germinal Center physiology
Humans
Molecular Sequence Data
Mutagenesis
Proto-Oncogene Proteins c-bcl-6
Burkitt Lymphoma genetics
Burkitt Lymphoma metabolism
Cytidine Deaminase genetics
Cytidine Deaminase metabolism
Genes, Immunoglobulin
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 54
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23399385
- Full Text :
- https://doi.org/10.1016/j.molimm.2013.01.005