Activation of complement pathways by univalent antibody derivatives with intact Fc zones.
The ability of two univalent antibody derivatives to invoke complement-mediated lysis of guinea-pig L2C leukemic lymphocytes was investigated. The derivatives were Fab/c from rabbit IgG antibody, in which only one Fab arm is removed from the parent molecule and FabFc in which Fab gamma, from peptic digestion of sheep IgG antibody, is disulfide-bonded to the Fc gamma yielded by papain digestion of an arbitrary IgG. Antibody activity was directed against surface IgM on the target cells. Both derivatives could invoke lysis via the classical pathway in the presence of rabbit complement. Exposure of the cells to the derivatives at 37 degrees C before introducing complement yielded no protective antigenic modulation. At low complement concns the derivatives were more efficient than the parent antibodies at invoking lysis, apparently due to the fact that the derivatives do not cause modulation: it appears that cells can undergo a useful degree of modulation when confronted simultaneously by bivalent antibody and low levels of complement. The Fab/c preparations were also able to invoke lysis by guinea-pig complement. Lysis occurred under conditions where activation took place only via the classical pathway (in dilute complement) or only via the alternative pathway (in the absence of calcium ions, or in C4-deficient guinea-pig serum). The results demonstrate that there is no need for two antigen-binding Fab arms in antibody activation of either the classical or alternative complement pathways. They favour models requiring clustering of Fc regions rather than steric changes which might follow binding of antigen.
D000818:Animals; D002460:Cell Line; D003167:Complement Activation; D003181:Complement C4 / Q000172:deficiency; D011416:Complement Factor D / Q000276:immunology; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003602:Cytotoxicity, Immunologic; D006168:Guinea Pigs; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007128:Immunoglobulin Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D011817:Rabbits
D003181:Complement C4; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011416:Complement Factor D