Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish, class switching at the μ locus

The IgH locus intronic enhancer (E(μ)), located in the intron between the J(H) segments and the C(μ) 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 E(μ) 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. Eμ/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 Eμ/MAR showed relatively normal switch frequency. These findings indicate that the Eμ/MAR region plays a significant, but not necessary role in facilitating class switching at the μ locus. Potential mechanisms for these findings are discussed.