C3 cleaved by membrane proteases binds to C3b acceptors expressed on concanavalin A-stimulated human lymphocytes and enhances antibody-dependent cellular cytotoxicity.
On activation of cells membrane-associated proteases--including serine esterases known to cleave the third component of complement (C3)--become expressed. In this paper it is shown that as a consequence of this enzyme activity isolated native human C3 added to concanavalin A (Con A)-activated human lymphocytes is cleaved on the surface of the blast cells. This enables the immediate fixation of nascent C3b (C3bx) through its short-lived metastable binding site to C3b acceptors (C3bA's) newly expressed on Con A-stimulated cells. Acceptor-bound C3b is detected by the immune adherence rosette formation of the C3-treated Con A blasts with the C3b receptor (C3bR)-bearing O, Rh+ erythrocytes (32 +/- 4%). The cleavage of C3 and the covalent fixation of C3b are shown to be inhibited by phenylmethylsulphonyl fluoride and methylamine, respectively. As a functional consequence of the covalent fixation of C3b to the mitogen-activated lymphocytes it is demonstrated that the antibody-dependent cellular cytotoxicity (ADCC) of these cells against O, Rh+ erythrocytes sensitized with anti-D IgG is significantly enhanced. The C3 specificity of the process and the role of C3bR's of the target cells are proved. It is postulated that effector cell-bound C3b amplifies ADCC by improving effector cell-target cell contact.
D000920:Antibody-Dependent Cell Cytotoxicity; D003176:Complement C3 / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D004789:Enzyme Activation; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism; D011951:Receptors, Complement / Q000276:immunology*; D017463:Receptors, Complement 3b; D011961:Receptors, Fc / Q000276:immunology; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D003176:Complement C3; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D003208:Concanavalin A; D003179:Complement C3b; D010447:Peptide Hydrolases