Strain Differences in Natural Killer Cell-mediated Immunity among Mice: A Possible Mechanism for the low Natural Killer Cell Activity of A/J Mice

Abstract

Natural killer (NK) cells are well established as fundamental elements in the early eradication of aberrant cells potentially leading to neoplasia. Moreover, it has also long been known that inbred strains of laboratory mice, as well as human individuals, demonstrate a wide range of NK cell-mediated immune response even to the same tumor. In the present study, various parameters which could lead ultimately to high, or low, NK cell-mediated functional activity have been assessed. Mice of the A/J strain demonstrate very low NK cell tumor-lytic activity and correspondingly high incidence of lymphoma. By contrast, C57B1/6 mice demonstrate relatively high NK cell activity and virtually never develop lymphomas. The results of this study have revealed that the absolute numbers of splenic NK cells were significantly lower in A/J vs C57B16/mice. Furthermore, the blood of A/J mice contained significantly fewer (30%) NK cells than did that of C57B1/6 mice. However, no significant difference between the 2 strains was found in the numbers of lymphocytic cells from NK cell-enriched fractions from the spleens, which possessed either the homing receptor MEL-14, or the integrin Mac-I, both essential surface molecules for transendothelial migration of lymphocytic cells from the circulation into organ parenchyma. Moreover, NK cells from both strains responded similarly to the NK cell stimulants, ATRA, indomethacin and interleukin-2. Finally, there was no significant difference between the 2 strains, in the numbers of lymphocytic cells in the bone marrow (including NK cells), which were radiolabelled with the DNA synthetic precursor, 3H-thymidine, indicative, thus, of equivalent levels of lymphocyte production by the bone marrow in the 2 strains. The observations collectively suggest that the low peripheral (spleen, blood) levels of NK cell-mediated functional activity found in the A/J strain of mouse at least, reflects either post-production, large-scale NK cell abortion/death, or a bone marrow-based microenvironmental deficiency which inhibits NK cells' exit from the bone marrow birth site.