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

This is the authors' abstract. We don't add key points for this paper.

In mature B cells, class switch recombination (CSR) replaces the expressed constant Cμ gene with a downstream CH gene. How the four transcriptional enhancers of the IgH 3′ regulatory region (3′RR) control CSR remains an open question. We have investigated IgG1 CSR in 3′RR-deficient mice. Here we show that the 3′RR enhancers target the Sγ1 acceptor region (and poorly the Sμ 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 Sμ-Sγ1 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. The molecular mechanisms of antibody class switching are incompletely understood. Here the authors show by using mice specifically lacking the IgH 3′ regulatory region enhancers that they prime the first steps of the class switch recombination.