DNA between variable and joining gene segments of immunoglobulin kappa light chain is frequently retained in cells that rearrange the kappa locus

A systematic analysis of the fate of the DNA between κ chain variable (V(κ)) and joining (J(κ)) genes in cells that have rearranged κ loci was carried out. The DNA from a variety of κ plasmacytomas, λ-producing hybridomas, and κ lymphocytes was digested, fractionated by size, and analyzed with two probes containing sequences 5' of J(κ). In 13 of 28 plasmacytomas examined the rearrangement of V(κ) and J(κ) appears to be acompanied by loss of DNA upstream of J(κ). However, in the rest of the plasmacytomas one or more upstream sequences are retained in a new context. In 9 of 12 λ-producing hybridomas (which frequently rearrange both κ loci) one or more upstream segments were detected. These unique fragments were probably generated by a recombination event near or at the J(κ) region. The extent to which the region between V and J is maintained in κ-expressing lymphocytes was also measured. Most (76%) of the region upstream of J(κ) is retained in the population, even though 68% of the κ loci are rearranged. In order to explain how these up-stream elements occur in some, but not all, cell lines, and the significant occurrence in the lymphocyte population, we propose a model in which a step in V-J joining involves mitotic recombination by unequal sister chromatid exchange.