Complement-mediated alteration of antibody specificity in vivo.

The simultaneous injection of heterologous anti-EL4 lymphoma serum and complement results in the rapid disappearance of such antibody from the periphery of non-tumor bearing mice. However, this phenomenon is only observed when a complement source capable of mediating the lysis of EL4 cells sensitized with such heterologous antibody is used. This complement mediated enhancement of anti-tumor antibody absorption was observed in vivo for three strains of mice. Omission of complement or the use of genetically deficient complement sources resulted in no effect on circulating antibody titer when compared to the titer of heterologous anti-tumor antibody observed in the periphery when injected alone. Exogenous complement did not enhance the clearance of heterologous anti-tetanus toxin serum, thereby suggesting that the increased absorption of anti-EL4 in vivo is not related simply to the enhanced clearance of foreign gamma-globulin. Confirmatory evidence of the role of complement in altering anti-tumor antibody specificity in vivo was obtained in a guinea pig tumor model as well. The data suggest that anti-tumor serum shown to be relatively specific for the tumor cell gains additional specificity in the presence of functional complement and consequently manifests avidity for cross-reactive determinants previously thought to be unrelated.