EXTENT TO WHICH HOMOLOGY CAN CONSTRAIN CODING EXON JUNCTIONAL DIVERSITY IN V(D)J RECOMBINATION

AMONG site-directed DNA recombination systems, V(D)J recombination is noteworthy in that identical reactants yield different recombination products at the junction of joined segments. This variation is the basis for diversity at the base of antigen receptor binding pockets and corresponds to V-(D)-J DNA junctions. An abundance of certain junctions has been noted1-5. It has been proposed that these junctions are favoured because they occur where short regions of homology in participating coding ends might align preferentially1. Here we use a system that is entirely free from cellular selection to show that the diversity of coding joints can be severely restricted when the coding ends participating in the reaction have short regions of homology. This constraint on diversity is diminished but not eliminated by terminal deoxynucleotidyl transferase, a mechanistic feature that has implications for the establishment of the immune repertoire.