The role of Fc-receptors in murine mercury-induced systemic autoimmunity.
Inorganic mercury (Hg) in genetically susceptible mouse strains induces a T cell-dependent, systemic autoimmune condition (HgIA) characterized by immunostimulation, anti-nuclear antibodies (ANA) and systemic immune-complex (IC) deposits. The exact phenotypic expression of HgIA in different strains depends on H-2 and non-H-2 genes. Fc receptors (FcRs) are important in the development of many autoimmune diseases. In this study, the effect of targeted mutations for activating and inhibiting FcRs in the BALB/c model of HgIA was examined. Hg-treated BALB/c mice without mutation (wild-type, wt) showed heavy IC deposits in the renal glomerular mesangium, as well as in renal and splenic vessel walls. The renal mesangial IC deposits were severely reduced in Hg-treated BALB/c mice without the gamma-chain (lack of the activating receptors FcgammaRI, FcgammaRIII and FcinRI), but unchanged in mice lacking the inhibitory FcgammaRIIB. The Hg-induced vessel wall IC deposits present in wt mice were abolished and reduced in the FcRgamma and FcgammaRIIB strains, respectively. Hg-treated BALB/c wt mice and mice without the gamma-chain showed an increase in serum IgE, while the increase in IgG1 was attenuated in the latter strain. In contrast, absence of the inhibiting FcgammaRIIB augmented the Hg-induced increase of both serum IgG1 and IgE. In conclusion, FcRs are important mainly for the induction of systmeic IC deposits in the HgIA model, but also affects serum IgG1 and IgE levels.
Martinsson
K
K
Division of Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linkoping University, SE-581 85 Linkoping, Sweden.
Hultman
P
P
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000936:Antigen-Antibody Complex / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002843:Chromatin / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005920:Glomerular Mesangium / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008628:Mercury; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D015415:Biomarkers; D002843:Chromatin; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D007073:Immunoglobulin E; D008628:Mercury