B-LINEAGE-RESTRICTED REARRANGEMENT OF A HUMAN IG-KAPPA TRANSGENE

To study the control of immunoglobulin kappa light chain gene rearrang ement, we generated transgenic mice carrying a germ-line human kappa m inilocus (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 a nd restricted to the B cell lineage. Quantification of kappa gene rear rangement in pre-B cell lines established from HK transgenic mice show ed that, like endogenous kappa genes, rearrangement of the transgene i s repressed in mu-negative early B cell precursors. These results indi cate 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 transge nic construct lacking the V-J intergenic region, suggests that this re gion, or elements associated with the proximal V gene, may act to rest rict kappa gene rearrangement to the B cell lineage.