Inverse correlation between natural antitumor antibodies and tumor susceptibility in individual xid-bearing mice

Natural antibodies (NAb), natural killer (NK) cells and activated macrophages have all been implicated in the rejection of threshold syngeneic tumor inocula. Previous analysis of tumor susceptibility in normal versus inbred and F1 mice bearing the B cell deficiency associated with the xid mutation of CBA/N mice demonstrated an inverse relationship between the tumorigenicity of the RI-28, a radiation-induced leukemia of the CBA/H strain, and the pooled anti-RI-28 serum NAb levels in mice with the same genetic origins. No relationship with tumor susceptibility was seen with NK cell or in vivo activated macrophage cytolysis. Flow-cytometric determination of antitumor serum NAb bled from individual male and female (CBA/N X CBA/J)F1 mice 1 week prior to the threshold tumor inoculation has revealed extensive heterogeneity within the NAb levels of each sex. A comparative analysis of tumor fate with NAb activity revealed that tumors appeared in only 26.3% of animals with a mean fluorescence channel binding above 60 channels in contrast with 77.3% of animals with lower NAb levels. These data extend to the level of individual hosts the support for an inverse relationship between host NAb activity and tumor susceptibility. In addition, subsequent analysis of serum antitumor NAb levels, splenic NK cytolysis and in vitro lymphokine-activated macrophage activity with all three mediators originating from the same individual F1 mice showed no consistent correlations between these natural resistance activities, arguing for the exclusion of deficiencies in NK cell or macrophage function as the basis for the differential tumor susceptibility in individual F1 mice.