B lineage-restricted rearrangement of a human Ig kappa transgene

To study the control of immunoglobulin kappa light chain gene rearrangement, we generated transgenic mice carrying a germ-line human kappa minilocus (HK) containing the J kappa-proximal V gene, V kappa IV, the V-J intergenic region, the five J kappa, segments and the C kappa gene. This construct includes the intronic, but not the 3' kappa enhancer. Rearrangement of the HK transgene was found to be lymphoid specific and restricted to the B cell lineage. Quantification of kappa gene rearrangement in pre-B cell lines established from HK transgenic mice showed that, like endogenous kappa genes, rearrangement of the transgene is repressed in mu-negative early B cell precursors. These results indicate that rearrangement of the HK transgene is subjected to the same B/T cell and developmental regulation as V kappa-J kappa rearrangement at the endogenous locus. Comparison with an unrearranged kappa transgenic construct lacking the V-J intergenic region, suggests that this region, or elements associated with the proximal V gene, may act to restrict kappa gene rearrangement to the B cell lineage.