Quantitative studies of the sensitivity of normal and neoplastic mouse cells to the cytotoxic action of isoantibodies.

Experiments were performed to study the mechanisms of the sensitivity of normal and neoplastic mouse cells to the cytotoxic action of humoral isoantibodies. A quantitative in vitro absorption procedure was used to compare the residua] hemagglutinin titer of a certain isoantiserum after the absorption of a known volume with known cell numbers. The cell numbers were adjusted so as to yield the same average total cell surface area. Lymph node cells and various solid and ascites tumor cells of strain A and C3H origin were used. It was found that different cell types differed with regard to their concentration of isoantigenic surface receptors. High correlation coefficients were found between the cytotoxic sensitivity and the concentration of isoantigenic receptors. It was shown that tumor cells which were partially or completely resistant to a single isoantiserum could be made sensitive to humoral isoantibodies provided that they were treated with mixtures of antisera, produced in different donor genotypes against the same target genotype, since each individual genotype reacts against a different antigen combination. This supports the concept that cytotoxic sensitivity is related to the surface concentration of reactive sites. Hematopoietic liver cells of newborn mice, which are completely resistant to isoantibodies, and spleen and lymph node cells of adult animals which are highly sensitive, were compared with regard to their ability to take up fluorescein-conjugated normal mouse serum in vitro. No differences were found between their visible pinocytotic uptake. Similar experiments were performed with various ascites tumor cells having different cytotoxic sensitivity. All tumor cells studied had a low pinocytosing ability which was not correlated to their sensitivity to humoral isoantibodies.