The receptor tyrosine kinase c-kit provides a critical signal for survival, expansion, and maturation of mouse natural killer cells

Fetal liver kinase ligands (flk2L/flt3L) and stem cell factor (SCF) have be en shown to promote natural killer (NK) cell differentiation from hematopoi etic stem cell (HSC) precursors in vitro. However, the contribution of sign aling through the receptors for these growth factors for in vivo NK cell de velopment remains ill-defined. We have analyzed the role of the SCF recepto r c-kit in NK cell differentiation by reconstituting NK-deficient mice with fetal liver (FL) HSCs of c-kit(-/-) (W/W) mice. Although c-kit(-/-)NK cell s were generated in W/W chimeras, they were reduced in number, contained a lower percentage of CD45R (B220)(+) cells, and were poorly cytolytic, In vi tro experiments showed that generation of NK cells from FL precursors was r educed in the absence of c-kit signaling and that SCF promoted the survival of peripheral c-kit(+) NK cells. We conclude that c-kit/SCF interactions i n vivo are dispensable for the commitment of HSC to the NK lineage, but the y provide essential signals for generating normal numbers of fully mature N K cells. (C) 2000 by The American Society of Hematology.