Productive immunoglobulin class-switch recombination (CSR) in activated B cells joins upstream switch μ-chain (Sμ) sequences to downstream Sγ, Sα or Sε segments. In Nature, Dong et al. provide a mechanistic basis for the deletional, rather than inversional, DNA recombination in the locus encoding the immunoglobulin heavy chain (Igh). High-throughput sequencing of 'bait' and 'prey' DNA junctions reveals a significant bias for DNA deletions in switching B cells. This deletional CSR bias is independent of the orientation of Sμ or its transcription. However, cells lacking 53BP1, a DNA-repair factor activated during CSR, lose directional recombination bias, as DNA inversions are as frequent as deletions. 53BP1 deficiency also increases the frequency of intra–switch-region 'resections', which likewise produce nonproductive CSR. Thus, 53BP1 enforces a directional bias during CSR to promote DNA deletions and thereby allow productive antibody switching from IgM to IgG, IgA or IgE.

Nature (26 August 2015) doi:10.1038/nature14970