Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Graninger, WB; Goldman, PL; Morton, CC; O'Brien, SJ; Korsmeyer, SJ.
The kappa-deleting element. Germline and rearranged, duplicated and dispersed forms.
J Exp Med. 1988; 167(2):488-501
Doi: 10.1084/jem.167.2.488
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- Führende Autor*innen der Med Uni Graz
- Graninger Winfried
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Alleles -
- Amino Acid Sequence -
- Base Sequence -
- Chromosome Deletion -
- Cloning, Molecular -
- Germ Cells - immunology
- Humans -
- Immunoglobulin Joining Region - genetics
- Immunoglobulin Variable Region - genetics
- Immunoglobulin kappa-Chains - genetics
- Molecular Sequence Data -
- Multigene Family -
- Recombination, Genetic -
- Transcription, Genetic -