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 o f bacteriophage Pl to generate a mouse strain in which the J(H) segmen ts and the intron enhancer in the IgH locus are deleted. By analysis o f immunoglobulin isotype switch recombination in heterozygous mutant B cells activated by lipopolysaccharide plus interleukin-4, we show tha t, on the mutant chromosome, switch recombination at the mu gene switc h region is strongly suppressed, whereas the switch region of the gamm a1 gene is efficiently rearranged. These data demonstrate an independe nt control of switch recombination at individual switch regions and su ggest that, in the process of switch recombination, the alignment of t he recombining strands occurs independently of and probably after the introduction of double-strand breaks into the switch regions involved.