The hemolysis of sensitized sheep erythrocytes in serum from guinea pigs with a total genetically controlled deficiency of C4 was studied with purified IgG and IgM anti-Forssman antibodies. It was found that an approximately 20-fold increase in hemolytic antibody concentration was necessary to initiate lysis in C4D serum as compared with normal serum. The kinetic curves of hemolysis in concentrated C4-deficient serum reached a plateau in 30 to 60 min. Lysis in the deficient serum could only be achieved with concentrated serum; hemolytic activity was rapidly lost on dilution. The lytic capacity of C4-deficient serum from individual animals was shown to vary markedly. The cytolytic reaction was specific in that only sensitized sheep erythrocytes were lysed, and there was no lysis of “innocent bystander” cells.

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