Interactions of monomeric IgG bearing covalently bound C3b with polymorphonuclear leucocytes.
The interactions of monomeric IgG, monomeric C3b, dimeric C3b, and C3b covalently bound to IgG (C3b-IgG) with neutrophils were examined. C3b-IgG heterodimers exhibited an increased affinity of binding to neutrophils, relative to C3b, both at half normal ionic strength (five-fold enhancement) and at normal ionic strength (six-fold enhancement). Binding of monomeric IgG to neutrophils was barely detectable and did not permit direct measurements of affinity in our assay conditions. The increased affinity of C3b-IgG for neutrophils was the result of divalent interactions with CR1, the C3b receptor, and the Fc gamma receptor of the cells, as could be demonstrated by competition studies using unlabelled IgG in the medium or monoclonal antibodies against the neutrophil Fc gamma receptor. This double receptor-ligand interaction allowed C3b-IgG to bind to the cells not only at normal ionic strength, but also in the presence of a 315-fold excess of IgG (near plasma concentration)--conditions that would preclude the binding of C3b or IgG alone. Furthermore, this interaction leads to the internalization of the C3b-IgG complex by the cells. C3b-IgG is internalized with kinetics similar to those found using dimeric C3b, with resting cells demonstrating a slow initial phase, which is accelerated by phorbol ester activation in both cases. Uptake of the homodimeric C3b was greater at 15 min than that of heterodimeric C3b-IgG, but both were significantly greater than that of monomer C3b, which showed no net internalization. The physiological implications of these findings are discussed.
D003179:Complement C3b / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007700:Kinetics; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D009994:Osmolar Concentration; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG
D007074:Immunoglobulin G; D010703:Phorbol Esters; D011961:Receptors, Fc; D017452:Receptors, IgG; D015240:Phorbol 12,13-Dibutyrate; D003179:Complement C3b