Direct in vivo VH to JH rearrangement violating the 12/23 rule

Abstract

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_HJ_H junctions, indicating that 23/23-guided recombination is possible, but is a low frequency event at the IgH locus in vivo.