Genetic Control of Murine Antibody-Dependent Cell-Mediated Cytotoxicity

We have observed that the intensity of the direct antibody-dependent cell-mediated cytotoxicity (ADCC) response after an inoculation of foreign tumour cells varies with the strain of mice studied. The inoculation of a human lymphoblastoid cell-line into CBA/J, BALB/c, or DBA/2 mice gives rise to a good cytotoxic response by the host K cells armed with specific antibodies. In contrast, A/J, B10.A, C57BL/6 and B10.S mice respond poorly under the same conditions. The high response is dominant in Fi hybrids between high and low responders and is also expressed among F2 backcrosses with the H-2 phenotype of low responders, suggesting that non-H-2 genes are also implicated in the regulation of ADCC. The genetic control is not exerted at the level of antibody secretion but at that of K-cell activity, since sera from high or low responders are equally effective in arming an ADCC reaction, whereas K cells from low-responder strains are less efficient than those from high-responder strains. The natural killer (NK) activity of the same strains has been screened. The results show a good correlation with some high- and low-responder strains, such as CBA and DBA/2 or A/J and SJL, respectively, but not with C57BL/6, B10.S or B10.A strains. Thus, in addition to common genes controlling both lytic functions, there are specific genetic factors influencing the balance between NK and K cells. These findings confirm the general view that NK and K cells represent only partially identical subsets.