Journal of Experimental Medicine, Vol 167, 488-501, Copyright © 1988 by Rockefeller University Press

ARTICLES

The kappa-deleting element. Germline and rearranged, duplicated and dispersed forms

WB Graninger, PL Goldman, CC Morton, SJ O'Brien and SJ Korsmeyer
Department of Medicine, Howard Hughes Medical Institute, St. Louis, Missouri 63110.

Human light chain genes are used in a kappa before lambda order. Accompanying this hierarchy is the rearrangement of a kappa-deleting element (Kde) which eliminates the kappa locus before lambda gene rearrangement. In approximately 60% of rearrangements the Kde recombines at a conserved heptamer within the J kappa-C kappa intron. We demonstrated that aberrant V/J rearrangements possessing apparent "N" nucleotides existed 5' to the J kappa-Kde rearrangements. This suggests that the Kde may selectively eliminate nonfunctional V/J alleles. A kappa-producing cell that displayed the unusual finding of lambda gene rearrangement demonstrated a rearranged Kde. This rearrangement was a V kappa/Kde recombination and the heptamer-11 bp spacer-nonamer flanking the V kappa is the target site of the Kde 40% of the time. The mouse possesses a counterpart to the Kde (recombining sequence [RS]) and the highly conserved regions surround the heptamer- spacer-nonamer signals. No complete protein product was predicted from the germline Kde near its break-point and no consistent fusion product was predicted from either the V/Kde or V/J-Kde rearrangements. A distal portion of the Kde is duplicated and is present at 2q11 as well as 2p11. The evolutionary conservation of the kappa-elimination event, the duplication and maintenance of the Kde indicates that it has a function. A portion of the Kde may still prove to encode a trans-acting factor that directly affects lambda rearrangement. A certain role for the Kde is its site-specific rearrangement, which destroys ineffective kappa genes and sets the stage for lambda gene utilization.
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