Direct in vivo V(H) to J(H) rearrangement violating the 12/23 rule

V(D)J recombination at the immunoglobulin heavy chain (IgH) locus follows the 12/23 rule to ensure the correct assembly of the variable region gene segments. Here, we report characterization of an in vivo model that allowed us to study recombination violating the 12/23 rule, namely a mouse strain lacking canonical D elements in its IgH locus. We demonstrate that V(H) to J(H) joining can support the generation of all B cell subsets. However, the process is inefficient in that B cells and antibodies derived from the D(H)-less allele are not detectable if the latter is combined with a wild-type IgH allele. There is no preferential usage of any particular V(H) gene family or J(H) element in V(H)J(H) junctions, indicating that 23/23-guided recombination is possible, but is a low frequency event at the IgH locus in vivo.