Class switch recombination (CSR) at the antibody immunoglobulin locus is regulated by germline transcription (GLT)-coupled modifications in the accessibility of the switch region, where CSR takes place. Here we show that histone acetylation of switch regions is linked to CSR but that histone acetylation cannot alone promote CSR or GLT. Activation-induced cytidine deaminase (AID) specifically associates with the CSR target chromatin in a GLT-coupled manner, which may occur potentially by means of physical interaction between AID and the transcription machinery. These data indicate an important role of GLT in the regulation of chromatin accessibility, strongly suggesting that the target of AID is chromatin DNA. Our results give insights on the role of AID and the regulatory mechanism of CSR.

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.