Antibody-Dependent Lymphoid Cell-Mediated Cytotoxicity: Role of Complement

Abstract

Unsensitized lymphoid cells have the capacity to destroy antibody-coated target cells in vitro. Definitive studies to rule out the participation of complement (C) components in this reaction require a system with a complete absence of C components and with no possibility of endogenous synthesis of C by cells in culture. Such a system is provided by using lymphoid effector cells from animals genetically deficient in certain C components and serum from these C-deficient animals to support the cultures. Lymphoid cells from animals genetically deficient in C4, C5 or C6 were found to be fully capable of destroying antibody-coated target burro erythrocytes. Direct C-mediated hemolysis of target cells via the classical or alternate pathways is thus ruled out. Furthermore, serum depleted of C3-9 by cobra venom factor treatment fully supported target cell lysis suggesting that the late C components derived from the serum are also not important. The role of the C3 receptor in promoting the binding of the effector cells to the antibody-coated targets was examined by competitive inhibition experiments. Whereas an excess of unrelated target cells coated with IgG inhibited cytotoxicity by competing for the aggregate receptor on the effector cell, coating of such competing cells with C in addition resulted in no further inhibition. Moreover an excess of unrelated target cells coated with IgM and C was not inhibitory. These findings indicate that the C3 receptor does not have a major role in this reaction in vitro.