C3 Cleaved by Membrane Proteases Binds to C3b Acceptors Expressed on Concanavalin A‐Stimulated Human Lymphocytes and Enhances Antibody‐Dependent Cellular Cytotoxicity

Abstract
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 cell. This enables the immediate fixation of nascent C3b (C3bx) through its short-lived metastable biinliniisite to Oh acceptors (C3bA's) newly expressed on Con A-stimulaled cells. Aeceptor-bound C3b is detected by the immune adherence rosette formation of the O-treated Con A blasts with the C3b receptor (C3bR)-bearing O. Rh+ erythroeytes (32 ± 4%). The cleavage of C3 and the covalent fixation of C3b are shown to he inhibited hy phenylmethylsulphonyl fluoride and methylamine, respeclively. As a functional consequence of the covalent fixation of C3b to the mitogen-activatcd 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.