When B cells, the antibody producing cells of the body, encounter antigen they switch from producing immunoglobulin (Ig) M to producing other classes of antibody (IgG, IgA or IgE), the class selected depending on the type of immune response needed. But the way in which B cells skillfully switch from one antibody class to another is still not clear although it is known to involve recombination between genes. In a Perspective, Stavnezer explains how formation of hybrids between RNA transcripts (transcribed from the heavy chain gene to which the cell will switch) and the DNA template at crucial switch sequences in the genome regulates class switching (Tracy et al.). It is possible that an as yet unidentified endonuclease digests the hybrid thereby creating the DNA ends that will be joined together.