IG S-GAMMA-3 DNA-SPECIFIC DOUBLE-STRAND BREAKS ARE INDUCED IN MITOGEN-ACTIVATED B-CELLS AND ARE IMPLICATED IN SWITCH RECOMBINATION

The looping-out and deletion model of switch recombination suggests th at double strand breaks (DSBs) may occur in switch regions and partici pate in the recombination transaction. A DSB assay based on the ligati on-mediated PCR method has been devised for the S gamma 3 region. Mito gen-inducible DSBs have been detected in S gamma 3 DNA of normal splen ic B cells but not in splenic T cells or thymocytes. The breaks are re stricted to the S gamma 3 region and are sequence specific, Examinatio n of the sequence surrounding the DSBs has led to the derivation of a consensus sequence for DSB formation. Induction of S gamma 3-specific DSBs is correlated with the onset of switch recombination. The DSBs fl ank clusters of S gamma 3 recombination breakpoints, suggesting that p rocessing of the broken ends may occur during the recombination reacti on.