BEIGE MUTATION IN THE MOUSE .1. STEM-CELL PREDETERMINED IMPAIRMENT IN NATURAL KILLER CELL-FUNCTION

Abstract

A point mutation, called beige [bg], on linkage group 14 in C57BL/6 mice leads to a marked impairment in natural killing [NK] and antibody-dependent, cell-mediated cytolysis (ADCC) of tumor cells. The defect in NK cytolysis was predetermined at the level of progenitor cells in the bone marrow as revealed in radiation chimeras. This impairment in NK function could not be accounted for by an altered organ distribution, target selectivity or ontogenesis. Interferon did not fully restore the response, which suggests that the defect may not result solely from a lack of endogenous interferon stimulation in bg mice. The frequency of target-binding cells was normal in all lymphoid organs, which suggests that the defect is intrinsic to the NK cell and does not involve an altered population size or an inability to recognize and interact with the target. The defect may lie within the lytic pathway subsequent to target cell contact. These mice should provide a useful NK-deficient system for studies of T [thymus-derived] cell or macrophage immunity and a means for testing the in vivo significance of NK cells in resistance to tumors and virus-infected cells.