An analysis of the natural killer cell defect in beige mice

Although C57BL/6 bg^J/bg^J mice exhibit very low or undetectable levels of endogenous natural killer cell activity, such activity can be induced by the administration of BCG or tilorone hydrochloride to these animals. This cytotoxic activity has been shown to be due to NK cells by the criteria of nylon-wool nonadherence and of effector cell sensitivity to treatment with either anti-asialo GM₁ serum or high concentrations of anti-Thy 1.2 serum, in the presence of complement. Even after the administration of inducing agents, however, beige mice continue to display significantly less NK activity than do their heterozygous littermates. In an attempt to ascertain what cell might be defective in responding to induction, we utilized an in vitro system in which the induction of NK activity by poly I:C in a nylon-wool nonadherent population is dependent upon plastic-adherent cells. We found that adherent cells from either beige or heterozygous mice were indistinguishable in their ability to restore the NK response of nylon-wool-nonadherent spleen cells stimulated with poly I:C. This was true when either beige or heterozygous mice were used as the source of responder cells. Thus, it appears that the defect in responsiveness to inducing agents may reside in the beige NK cell itself.