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 F₁ 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. [ABSTRACT FROM AUTHOR]