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

Abstract

A systematic analysis of the fate of the DNA between kappa chain variable (V kappa) and joining (J kappa) genes in cells that have rearranged kappa loci was carried out. The DNA from a variety of kappa-producing plasmacytomas, lambda-producing hybridomas, and kappa-expressing lymphocytes was digested, fractionated by size, and analyzed with two probes containing sequences 5' of J kappa. In 13 of 28 plasmacytomas examined the rearrangement of V kappa and J kappa appears to be accompanied by loss of DNA upstream of J kappa. However, in the rest of the plasmacytomas one or more upstream sequences are retained in a new context. In 9 of 12 lambda-producing hybridomas (which frequently rearrange both kappa loci) one or more upstream segments were detected. These unique fragments were probably generated by a recombination event near or at the J kappa region. The extent to which the region between V and J is maintained in kappa-expression lymphocytes was also measured. Most (76%) of the region upstream of J kappa is retained in the population, even though 68% of the kappa loci are rearranged. In order to explain how these upstream 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.