Format

Send to:

Choose Destination
See comment in PubMed Commons below
Blood. 2005 May 1;105(9):3521-7. Epub 2005 Jan 13.

Jagged2 promotes the development of natural killer cells and the establishment of functional natural killer cell lines.

Author information

  • 1Division of Hematology, Department of Medicine, University of Utah, Salt Lake City, UT, USA.

Abstract

Emerging evidence indicates that Notch receptors and their ligands play important roles in the development of T cells and B cells. However, little is known about their possible roles in the development of other lymphoid cells. Here we demonstrate that Jagged2, a Notch ligand, stimulates the development of natural killer (NK) cells from Lin(-) Sca-1(+) c-kit(+) hematopoietic stem cells. Our culture system supports NK cell development for 2 to 3 months, often leading to the establishment of continuous NK cell lines. The prototype of such cell lines is designated as KIL. KIL depends on interleukin-7 for survival and proliferation and is NK1.1(+) CD3(-) TCRalphabeta(-) TCRdeltagamma(-) CD4(-) CD8(-) CD19(-) CD25(+) CD43(+) CD45(+) CD49b(-) CD51(+) CD94(+) NKG2D(+) Mac-1(-/low) B220(-) c-kit(+) perforin I(+) granzyme B(+) Notch-1(+), and cytotoxic. Like normal natural killer cells, the T-cell receptor-beta loci of KIL remain in the germ-line configuration. In response to interleukin-2, KIL proliferates extensively (increasing cell number by approximately 10(10)-fold) and terminally differentiates into adherent, hypergranular NK cells. Our findings indicate that Jagged2 stimulates the development of natural killer cells and the KIL cell line preserves most properties of the normal NK precursors. As such, KIL provides a valuable model system for NK cell research.

PMID:
15650053
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk