IgG immune complex-binding in macrophages from arthritis-susceptible and arthritis-resistant mice following collagen type II immunization.
Occupancy of Fc gamma receptors (FcgammaR) by immune complexes (IC) induces secretion of various inflammatory mediators and cytokines. Therefore, knowledge of the FcR function is fundamental for understanding inflammatory processes. Here, we report an alteration in the FcR function in collagen-induced arthritis (CIA). The FcgammaR-binding activity of peritoneal macrophages from arthritis-susceptible DBA/1 mice following collagen type II (CII)/CFA immunization was assessed by Fc rosetting of SRBC opsonized with different IgG subclasses. A progressive reduction of IgG1 IC-binding was observed after immunization, and by the time of arthritis onset, the IgG1 IC-binding was abolished. Binding of IgG2a or IgG2b IC, however, was not affected. The blocked IgG1 IC-binding was reversed by a prior mild acid wash of the CIA macrophages, indicating receptor occupancy as the cause of the blocked binding. The impaired IgG1 IC-binding was associated with arthritis development, as macrophages from CII/CFA-immunized, arthritis-resistant SWR mice or DBA/1 mice, immunized with CFA alone, did not show this effect. Normal DBA/1 macrophages, blocked with a monoclonal antibody to FcgammaRIIB/FcgammaRIII, and macrophages from FcgammaRIII-deficient mice did not bind IgG1 IC, indicating FcgammaRIII as responsible for IgG1 IC-binding. Our data suggest that an increased degree of saturation of FcgammaRIII precedes the development of CIA, which is reflected by a reduced IgG1 IC-binding in macrophages of CII/CFA-immunized DBA/1 mice.
Thorvaldson
L
L
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Fuchs
D
D
Magnusson
S
S
Kleinau
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology; D020022:Genetic Predisposition to Disease; D007074:Immunoglobulin G / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D024043:Collagen Type II; C499172:Fcgr2b protein, mouse; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG