International Immunology, Vol 10, 1121-1129, Copyright © 1998 by Oxford University Press
MM Lin, NS Green, W Zhang and MD Scharff
The Ig kappa intronic and 3'kappa light chain enhancers have been shown to
be necessary for V region hypermutation in kappa light chain transgenes. To
investigate the role of the E mu intronic enhancer in V region
hypermutation of heavy chain genes, E mu and its associated matrix
attachment regions (MAR) were replaced with the SV40 or the cytomegalovirus
(CMV) enhancer in a gamma2a construct that hypermutates its rearranged VDJ
region in the NSO plasmacytoma and 18.81 pre-B cell lines. In this model in
vitro system, mutation rates of stable transfectants were determined by
reversion analysis using a V region stop codon that, when mutated, allowed
the detection of cellular revertants by ELISA spot assay. The gamma2a
constructs with the E mu, SV40 and CMV enhancers mutated at comparably high
rates in the B cell lines, but not in L cells, indicating that the E mu
enhancer and its associated MAR were not specifically required for IgH
hypermutation in this system. In parallel experiments, the addition of the
3'alpha heavy chain enhancer (hs 1,2) or the 3'kappa light chain enhancer
did not increase the mutation rate of a related mu reporter construct in
which the associated VDJ mutates at a moderately low rate in NSO cells or
in cell hybrids made between 18.81 and NSO. These results imply that cis-
acting IgH elements that promote hypermutation may not be restricted to
Ig-specific transcriptional enhancers.
ARTICLES
The effects of E mu, 3'alpha (hs 1,2) and 3'kappa enhancers on mutation of an Ig-VDJ-Cgamma2a Ig heavy gene in cultured B cells
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
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