Heterogeneity in the ability of cytotoxic murine NK cell clones to enhanceIg secretion in vitro

We recently described a panel of cytotoxic murine NK cell clones that also enhanced Ig secretion by B cells activated in an in vitro model of T cell-i ndependent type 2 (TI-2) responses, We employed dextran-conjugated anti-IgD (alpha delta-dex) as a model antigen, Here we study the mechanism of Ig in duction by these clones. Addition of the various NK clones to sort-purified B cells stimulated with alpha delta-dex and IL-2 resulted in a markedly he terogeneous increase in Ig secretion, which varied from 3-fold, as mediated by clone PKO 56, to 15-fold, as induced by clone PKO 101. The other NK cel ls showed intermediate levels of Ig induction. Furthermore, while addition of as few as 0.04% of PKO 101 cells stimulated significant increases and 1% induced near maximum Ig production, a 3% addition of PKO 56 cells was requ ired for significant enhancement of Ig secretion. Supernatant material coll ected from the NK clones mediated Ig production at levels that mirrored the induction by the corresponding cells. Cytokine analysis showed that while all members of the NK panel produced IFN-gamma, only two secreted granulocy te macrophage colony stimulating factor and that the levels of Ig induction mediated by the NK clones correlated only with their levels of IFN-gamma s ecretion. Culture of a and NK cells in the presence of anti-IFN-gamma demon strated that IFN-gamma was the critical cytokine in NK-induced Ig productio n. These findings establish heterogeneity in the ability of NK cells to inc rease Ig secretion in vitro and show that NK-produced IFN-gamma. is an impo rtant factor in determining this heterogeneity.