Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish, class switching at the mu locus.
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.
The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
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A
Bottaro
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F
Young
J
J
Chen
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M
Serwe
F
F
Sablitzky
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FW
Alt
D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015152:Blotting, Northern; D015139:Blotting, Southern; D017353:Gene Deletion; D006825:Hybridomas / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007438:Introns; D051379:Mice
D007143:Immunoglobulin Heavy Chains