Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells

Noelle Sevilir Williams, Jennifer Klem, Igor J. Puzanov, P. V. Sivakumar, Michael Bennett, Vinay Kumar

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Abstract

To delineate factors involved in NK cell development, we established an in vitro system in which lineage marker (Lin)-, c.kit+, Sca2+ bone marrow cells differentiate into lyric NK1.1+ but Ly49- cells upon culture in IL-7, stem cell factor (SCF), and flt3 ligand (flt3L), followed by IL-15 alone. A comparison of the ability of IL-7, SCF, and flt3L to generate IL-15- responsive precursors suggested that NK progenitors express the receptor for flt3L. In support of this, when Lin-, c-kit+, flt3+ or Lin-, c-kit+, flt3- progenitors were utilized, 3-fold more NK cells arose from the flt3+ than from the flt3- progenitors. Furthermore, NK cells that arose from flt3- progenitors showed an immature NK1.1(dim), CD2-, c-kit+ phenotype as compared with the more mature NK1.1(bright), CD2(+/-), c-kit- phenotype displayed by NK cells derived from flt3+ progenitors. Both progenitors, however, gave rise to NK cells that were Ly49 negative. To test the hypothesis that additional marrow-derived signals are necessary for Ly49 expression on developing NK cells, flt3+ progenitors were grown in IL-7, SCF, and flt3L followed by culture with IL-15 and a marrow-derived stromal cell line. Expression of Ly49 molecules, including those of which the MHC class I ligands were expressed on the stromal or progenitor cells, as well as others of which the known ligands were absent, was induced within 6-13 days. Thus, we have established an in vitro system in which Ly49 expression on developing NK cells can be analyzed and possibly experimentally manipulated.

Original languageEnglish (US)
Pages (from-to)2648-2656
Number of pages9
JournalJournal of Immunology
Volume163
Issue number5
StatePublished - Sep 1 1999

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Natural Killer Cells
Stem Cells
Bone Marrow
Interleukin-15
Interleukin-7
Stem Cell Factor
Stromal Cells
Ligands
Phenotype
Bone Marrow Cells
Cell Culture Techniques
Cell Line
flt3 ligand protein

ASJC Scopus subject areas

  • Immunology

Cite this

Williams, N. S., Klem, J., Puzanov, I. J., Sivakumar, P. V., Bennett, M., & Kumar, V. (1999). Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells. Journal of Immunology, 163(5), 2648-2656.

Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells. / Williams, Noelle Sevilir; Klem, Jennifer; Puzanov, Igor J.; Sivakumar, P. V.; Bennett, Michael; Kumar, Vinay.

In: Journal of Immunology, Vol. 163, No. 5, 01.09.1999, p. 2648-2656.

Research output: Contribution to journalArticle

Williams, NS, Klem, J, Puzanov, IJ, Sivakumar, PV, Bennett, M & Kumar, V 1999, 'Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells', Journal of Immunology, vol. 163, no. 5, pp. 2648-2656.
Williams NS, Klem J, Puzanov IJ, Sivakumar PV, Bennett M, Kumar V. Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells. Journal of Immunology. 1999 Sep 1;163(5):2648-2656.
Williams, Noelle Sevilir ; Klem, Jennifer ; Puzanov, Igor J. ; Sivakumar, P. V. ; Bennett, Michael ; Kumar, Vinay. / Differentiation of Nk1.1+, Ly49+ NK cells from flt3+ multipotent marrow progenitor cells. In: Journal of Immunology. 1999 ; Vol. 163, No. 5. pp. 2648-2656.
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