International Immunology, Vol 10, 799-806, Copyright © 1998 by Oxford University Press
A Bottaro, F Young, J Chen, M Serwe, F Sablitzky and FW Alt
The IgH locus intronic enhancer (Emu), located in the intron between the
J(H) segments and the Cmu gene, and flanked by two matrix attachment
regions (MAR), has been shown to be a major regulator of IgH gene
transcription and VDJ recombination. To define the potential role of Emu
plus MAR in class switch recombination (CSR), we generated IgG- expressing
hybridomas from B cells heterozygous for mutations that delete all of these
elements or replace them with a neo(r) gene and analyzed the switch status
of the mutated IgH loci. Emu/MAR-deleted IgH loci displayed a highly
significant, although not complete, decrease in CSR when compared to
unmutated loci in normal hybridomas. Surprisingly, mutant loci with a pgk
promoter-driven neo(r) gene replacing the Emu/MAR showed relatively normal
switch frequency. These findings indicate that the Emu/MAR region plays a
significant, but not necessary role in facilitating class switching at the
mu locus. Potential mechanisms for these findings are discussed.
ARTICLES
Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish, class switching at the mu locus
The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
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