Elucidation of IgH 3 ' region regulatory role during class switch recombination via germline deletion

摘要

In mature B cells, class switch recombination (CSR) replaces the expressed constant C mu gene with a downstream C-H gene. How the four transcriptional enhancers of the IgH 3' regulatory region (3'RR) control CSR remains an open question. We have investigated IgG(1) CSR in 3'RR-deficient mice. Here we show that the 3'RR enhancers target the S-gamma 1 acceptor region (and poorly the S-mu donor region) by acting on epigenetic marks, germline transcription, paused RNA Pol II recruitment, R loop formation, AID targeting and double-strand break generation. In contrast, location and diversity of S-mu-S-gamma 1 junctions are not affected by deletion of the 3'RR enhancers. Thus, the 3'RR controls the first steps of CSR by priming the S acceptor region but is not implicated in the choice of the end-joining pathway.