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 response^1–3. 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 C_H2 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 C_H2 regions but lacks the C_H3 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 C_H3 region of the molecule. In view of these conflicting reports we have investigated the possible role of the C_H3 region of human IgG in binding to homologous monocytes.