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.