C-3 CLEAVED BY MEMBRANE PROTEASES BINDS TO C3B ACCEPTORS EXPRESSED ON CONCANAVALIN-A-STIMULATED HUMAN-LYMPHOCYTES AND ENHANCES ANTIBODY-DEPENDENT CELLULAR CYTO-TOXICITY

On activation of cells membrane-associated proteases, including serine esterases known to cleave the 3rd component of complement (C3), become expressed. 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) 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 phenylmethylsulfonyl 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 of the target cells are proved. It is postulated that effector cell-bound C3b amplifies ADCC by improving effector cell-target cell contact.