Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression

In the mouse, two families of MHC class I-specific receptors, namely Ly49 a nd CD94/NKG2, have been identified on NK cells. Individual NK cells can exp ress several Ly49 molecules as well as members of the CD94/NKG2 family. The expression of multiple receptors with different specificities for MHC clas s I is thus thought to generate NK cells with diverse recognition patterns. To delineate the mechanism by which NK cells begin to express different pa tterns of Ly49 and CD94/NKG2 molecules, we developed a clonal assay in whic h NK1.1(-), IL-2/IL-15 receptor beta(+) NK precursors generated by culture of multipotential Lin(-), c-kit(+) progenitors in IL-7, stem cell factor an d flt3 ligand are induced to differentiate into NK1.1(+), Ly49(+) NK cells. Examination of the clonal populations thus generated revealed heterogeneit y in the pattern of Ly49 and CD94/NKG2 gene expression. In addition, a dist inct kinetic pattern of expression was observed. CD94, NKG2A, NKG2C and Ly4 9B were expressed first followed by Ly49G, then Ly49C and I and finally, Ly 49A, D, E and F. The data suggest a stochastic but ordered acquisition of c lass I receptors on NK cells in which developing NK cells become capable of expressing distinct receptors at different times but show no absolute prer equisite to express the receptors that are acquired early in NK development for the expression of those that are acquired later.