Differentiation of Ly49s-positive or -negative natural killer cells is inhibited by anti-H-2(b) monoclonal antibodies acting at the level of bone marrow progenitors from B6 mice

To investigate the role of MHC class I on in vitro differentiation of natur al killer (NK) cells, a CD44(low/-)CD2(-)classl(low) population was isolate d from mouse bone marrow. This population, which lacked expression of NK-1. 1, Ly49A, Ly49C/l, and Ly49G, generated populations of NK-1.1(+) NK cells e xpressing Ly49A, Ly49C/l, or Ly49G when cocultured for 13 days with syngene ic supportive stromal cells in the presence of interleukin 2. Ly49A and Ly4 9C/l were absent on the progeny of progenitors tested after 7 days of cultu re but were expressed as a late event together with low-level expression of NK-1.1, from day 8 of culture, the addition of anti-H-2(b) monoclonal anti body to cultures at day 0 inhibited proliferation of progenitors supported by either syngeneic, allogeneic, or H-2(b)-deficient stromal cells, thus su ggesting that the effect was not exerted on stromal cells. Additional analy ses demonstrated that class l(low) progenitors generated class I+ cells on which the anti-H-2b monoclonal antibody exerted its inhibitory effect.