Localisation of monocyte binding site of human immunoglobulin G.

Abstract

THE binding of IgG to macrophages is thought to be important in both the afferent and efferent limbs of the immune response1–3. Berken and Benacerraf4 studied the properties of guinea pig IgG2 antibodies cytophilic for macrophages and concluded that the binding site was in the Fc region. Similarly Lo Buglio et al.5 and Abramson et al.6 inhibited with isolated Fc fragment the binding of human monocytes to red cells coated with anti-D. Abramson et al.6 also studied the inhibitory activity of various fragments obtained by peptic digestion of IgG. The F(ab′)2 fragment was slightly inhibitory, unlike Fab fragment, and the authors suggested that the binding site was in the N-terminal portion of the Fc fragment (now known as the CH2 region). Huber and Fudenberg7 reached similar conclusions following experiments in which F(ab′)2 fragments of anti-D antibodies were attached to red blood cells and produced rosettes with human monocytes, although the possibility of contaminating IgG could not be eliminated. In contrast, MacLennan et al.8 were unable to inhibit neutrophil phagocytosis of sensitised bacteria with immune complexes of antigen and the Facb fragment of rabbit IgG. Since the Facb fragment includes the Fab and CH2 regions but lacks the CH3 region this suggests that the latter may be the site of neutrophil binding. Furthermore, Yasmeen et al.9, working with a heterologous system (human immunoglobulin G and guinea pig macrophages) have presented evidence that macrophage binding is a property of the CH3 region of the molecule. In view of these conflicting reports we have investigated the possible role of the CH3 region of human IgG in binding to homologous monocytes.