Target specificity of immunoglobulin class switch recombination is not determined by nucleotide sequences of S regions.

We describe a model system for class switch recombination (CSR) using CH12F3-2 cells transfected with a DNA construct containing two S sequences transcribed by different promoters and separated by a viral thymidine kinase (TK) gene. Recombination observed using this system shares key properties with physiological CSR: deletion of DNA between two S regions, requirement for cytokine stimulation, and nonhomologous and no consensus breakpoint sequences. Studies on transfectants with variants of this construct led us to the following conclusions: (1) two S sequences are required for CSR; (2) isotype specificity of recombination is not determined by nucleotide sequences of S regions; (3) S sequences are not strand-specific; and (4) induction of recombination activity requires cytokine stimulation.