Journal
MOLECULAR IMMUNOLOGY
Volume 45, Issue 13, Pages 3600-3608Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2008.05.012
Keywords
somatic hypermutation; DNA secondary structures; transcription; VH genes; computer model
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Funding
- NIH [R01CA099242]
- Stella Duncan Memorial Research Institute
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The role of secondary structures and base mutability at different levels of transcription and supercoiling is analyzed in variable region antibody genes VH5, VH94 and VH186.2. The data are consistent with a model of somatic hypermutation in which increasing levels of transcription and secondary structure stability correlate with the initial formation of successive mutable sites. Encoded differences exist in stem length and the number of GC pairs at low versus high levels of transcription in CDRs. These circumstances simplify the complexities of coordinating mutagenesis by confining this process to each mutable site successively, as they form in response to increasing levels of transcription during affinity maturation. (C) 2008 Elsevier Ltd. All rights reserved.
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