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PMID: 1756738 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication.

The EMBO journal ·Vol. 10 ·No. 13 ·1991-12-00 ·Pages 4331-41

Rogerson B, Hackett J, Peters A, Haasch D, Storb U

Abstract

We have previously demonstrated that B lymphocyte specific somatic mutations are introduced into the variable regions of immunoglobulin kappa transgenes in two independent transgenic mouse lines. The frequency, distribution and nature of these mutations strongly suggest that they arose as a result of the process of somatic hypermutation, which is responsible, in part, for affinity maturation during an immune response. Unexpectedly, in these multiple copy transgenic lines, many of the transgene copies showed no evidence of somatic mutation. This paradox was addressed by determining the sequence of each transgene copy in several B cell hybridomas derived from a mouse line carrying three copies of the kappa transgene. It was found that the somatic hypermutation process in different B cells from the same mouse preferentially targets one, but not the same, transgene copy. We present a model, based on the pattern of this targeting, which links somatic hypermutation to the orientation of the Ig gene relative to the direction of DNA replication.

MeSH Terms
Animals Base Sequence DNA/genetics DNA Replication Genes, Immunoglobulin Hybridomas Immunoglobulin Variable Region/genetics Immunoglobulin kappa-Chains/genetics Mice Mice, Transgenic Molecular Sequence Data Mutation Plasmids Polymerase Chain Reaction Transcription, Genetic
Chemicals
Immunoglobulin Variable Region Immunoglobulin kappa-Chains DNA
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rogerson B
Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637.
Hackett J
Peters A
Haasch D
Storb U
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1991-12-00
Pages
4331-41
Language
English
Region
England
NLM ID
8208664
PMCID
PMC453186
Subset
IM
Grants
NIGMS NIH HHS · GM38649 · United States
NICHD NIH HHS · HD23089 · United States
External Links
PubMed source PMC Full Text View journal details
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