STIMULATION OF KAPPA LIGHT-CHAIN GENE REARRANGEMENT BY THE IMMUNOGLOBULIN MU HEAVY-CHAIN IN A PRE-B-CELL LINE

B-lymphocyte development exhibits a characteristic order of immunoglob ulin gene rearrangements. Previous work has led to the hypothesis that expression of the immunoglobulin mu heavy chain induces rearrangement activity at the kappa light-chain locus. To examine this issue in mor e detail, we isolated five matched pairs of mu- and endogenously rearr anged mu+ cell lines from the Abelson murine leukemia virus-transforme d pro-B-cell line K.40. In four of the five mu+ cell lines, substantia l expression of mu protein on the cell surface was observed, and this correlated with an enhanced frequency of kappa immunoglobulin gene rea rrangement compared with that in the matched mu- cell lines. This incr eased kappa gene rearrangement frequency was not due to a general incr ease in the amount of V(D)J recombinase activity in the mu- cells. Con sistently, introduction of a functionally rearranged mu gene into one of the mu- pre-B-cell lines resulted in a fivefold increase in kappa g ene rearrangements. In three of the four clonally matched pairs with i ncreased kappa gene rearrangements, the increase in rearrangement freq uency was not accompanied by a significant increase in germ line trans cripts from the C. locus. However, in the fourth pair, K.40D, we obser ved an increase in germ line transcription of the K locUS after expres sion of mu protein encoded by either an endogenously rearranged or a t ransfected functional heavy-chain allele. In these cells, the amount o f the germ line C(kappa) transcript correlated with the measured frequ ency of rearranged kappa genes. These results support a regulated mode l of B-cell development in which mu protein expression in some way tar gets the V(D)J recombinase to the kappa gene locus.