Variation in the crossover point of kappa immunoglobulin gene V-J recombination: evidence from a cryptic gene

Analysis of amino acid and nucleotide sequences of kappa immunoglobulin chains and their genes has led to the hypothesis that the exact site of V-J joining in these genes varies and that this variation is partially responsible for generating amino acid diversity at the recombination site. To assess this hypothesis we have cloned and determined the sequence of one of the two V-J recombinant genes carried by the plasmacytoma MOPC173 and the V region germline precursor of this gene. We find that this V region has been joined to a J segment at a crossover point that indeed differs from the one previously described. This recombination has occurred in such a way as to produce an out of phase, missense reading frame and, hence, a cryptic light chain gene. This result directly supports the cross-over-point variation hypothesis but also indicates that the flexibility of this reaction is accompanied by a cost to the organism in terms of the generation of missense genes.