IL-2-driven natural killer cell generation: Role of anti-H-2(b) monoclonalantibodies and stromal cells in controlling quantitative and repertoire changes

To investigate the role of major histocompatibility complex class I and bon e marrow stromal cells on in vitro differentiation of natural killer cells, a CD44(low)/(-)CD2(-) population was isolated from mouse bone marrow. This NK-1.1(-)CD3(-)LFA-3(+)B220(+) population, when stimulated with IL-2 and c o-cultured with supportive syngeneic stromal cells, generated populations o f NK-1.1(+)Ly49A(+)Ly49C/I(+)CD3(-) mature natural killer cells. The effect of anti-H-2(b) monoclonal antibodies (mAbs) on this phenomenon was assayed . Pre-adhesion of anti-H-2(b) mAbs to the stromal cells did not exert any e ffect, whereas when the same mAbs were pre-adhered to progenitors, there wa s a inhibition of natural killer cell generation that was maximum when the mAbs were added directly to cultures. In addition, the anti-H-2(b) mAbs did not inhibit the IL-2-induced proliferation of mature natural killer cells. Allogeneic but not H-2(b)-deficient stromal cells decreased the expression of Ly-49C/I but not Ly49A, thus suggesting that stromal cell haplotypes qu alitatively influence the expression of Ly49s repertoire.