INDEPENDENT CONTROL OF IMMUNOGLOBULIN SWITCH RECOMBINATION AT INDIVIDUAL SWITCH REGIONS EVIDENCED THROUGH CRE-IOXP-MEDIATED GENE TARGETING

We have employed a method based on the Cre-IoxP recombination system of bacteriophage Pl to generate a mouse strain in which the J(H) segments and the intron enhancer in the IgH locus are deleted. By analysis of immunoglobulin isotype switch recombination in heterozygous mutant B cells activated by lipopolysaccharide plus interleukin-4, we show that, on the mutant chromosome, switch recombination at the mu gene switch region is strongly suppressed, whereas the switch region of the gamma1 gene is efficiently rearranged. These data demonstrate an independent control of switch recombination at individual switch regions and suggest that, in the process of switch recombination, the alignment of the recombining strands occurs independently of and probably after the introduction of double-strand breaks into the switch regions involved.