IL-2-driven natural killer cell generation: role of anti-H-2b monoclonal antibodies and stromal cells in controlling quantitative and repertoire changes.

摘要

To investigate the role of major histocompatibility complex class I and bone 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 co-cultured with supportive syngeneic stromal cells, generated populations of NK-1.1+ Ly49A+ Ly49C/I+ CD3- mature natural killer cells. The effect of anti-H-2b monoclonal antibodies (mAbs) on this phenomenon was assayed. Pre-adhesion of anti-H-2b mAbs to the stromal cells did not exert any effect, whereas when the same mAbs were pre-adhered to progenitors, there was a inhibition of natural killer cell generation that was maximum when the mAbs were added directly to cultures. In addition, the anti-H-2b mAbs did not inhibit the IL-2-induced proliferation of mature natural killer cells. Allogeneic but not H-2b-deficient stromal cells decreased the expression of Ly-49C/I but not Ly49A, thus suggesting that stromal cell haplotypes qualitatively influence the expression of Ly49s repertoire.