Clonal acquisition of inhibitory Ly49 receptors on developing NK cells is successively restricted and regulated by stromal class I MHC

We report an in vitro stroma-dependent system for the clonal growth and dif ferentiation of natural killer (NK) cells from lymphoid-restricted bone mar row progenitors or bone marrow NK1.1(+) cells. Strikingly, the potential to initiate expression of specific Ly49 receptors becomes increasingly restri cted as NK cells develop. Moreover, when NK cells express a Ly49 receptor s pecific for stromal cell class I MHC, they are less likely to initiate expr ession of another Ly49 receptor in the clonal culture system. The results i ndicate multiple roles for stromal cells in NK cell development, in support ing clonal growth, in initiation of Ly49 receptor expression, and in format ion of the NK cell receptor repertoire.