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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 Mice¹

Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Perugia, 06100 Perugia, Italy [D. V. D., B. D. M., E. A., G. N., S. B., C. R.]; Karolinska Institute MTC, Stockholm, Sweden [M. S., H-G. L.]; and Department Scienza del Farmaco, University G. D’Annunzio, 66100 Chieti, Italy [L. B.]

Abstract

To investigate the role of MHC class I on in vitro differentiation of natural killer (NK) cells, a CD44^low/-CD2^-classI^low population was isolated from mouse bone marrow. This population, which lacked expression of NK-1.1, Ly49A, Ly49C/I, and Ly49G, generated populations of NK-1.1⁺ NK cells expressing Ly49A, Ly49C/I, or Ly49G when cocultured for 13 days with syngeneic supportive stromal cells in the presence of interleukin 2. Ly49A and Ly49C/I were absent on the progeny of progenitors tested after 7 days of culture 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 antibody to cultures at day 0 inhibited proliferation of progenitors supported by either syngeneic, allogeneic, or H-2^b-deficient stromal cells, thus suggesting that the effect was not exerted on stromal cells. Additional analyses demonstrated that class I^low progenitors generated class I⁺ cells on which the anti-H-2^b monoclonal antibody exerted its inhibitory effect.