The effect of activating and inhibiting Fc-receptors on murine mercury-induced autoimmunity.
Fc-receptors for IgG (FcgammaR) link cellular and humoral immune responses, controlling the balance between activating and inhibitory immune responses, and are involved in autoimmune diseases. Mercury (Hg) induces an autoimmune condition in genetically (H-2(s,q,f)) susceptible mice characterized by lymphoproliferation, hypergammaglobulinemia and IgG antinucleolar antibodies (ANoA). Here we investigate the role of activating (FcgammaRI, FcgammaRIII) and inhibitory (FcgammaRIIb) Fc-receptors on mercury-induced autoimmunity (HgIA) using DBA/1 mice (H-2(q)) with targeted FcgammaR mutations and wild type (wt) mice. Mice deficient for the FcRgamma-chain or FcgammaRIII and treated with 15 mg/L HgCl(2) showed a delayed and attenuated IgG1, IgG2a and IgG2b ANoA response compared to wt mice. Female Hg-treated FcgammaRIIB(-/-) mice showed a significant increased of IgG2b ANoA development compared to wt mice. The total serum IgG1 response due to Hg was attenuated in FcRgamma(-/-) and FcgammaRIII(-/-) mice compared to wt mice. Hg-treated FcgammaRIIB(-/-) mice showed an increase of both serum IgG1 and IgE compared to wt mice. We conclude that FcgammaRIII is of importance for the rapidity and final strength of the ANoA response and the increase in serum IgG1 in HgIA, while lack of FcgammaRIIb increases the IgG2b ANoA response and the serum IgG1 and IgE response.
Martinsson
Klara
K
Division of Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linköping University, Linköping, Sweden.
Carlsson
Louise
L
Kleinau
Sandra
S
Hultman
Per
P
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood* / Q000235:genetics / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000235:genetics*; D004195:Disease Models, Animal; D025461:Feedback, Physiological / Q000235:genetics / Q000276:immunology*; D005260:Female; D006942:Hypergammaglobulinemia / Q000097:blood / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D008627:Mercuric Chloride / Q000633:toxicity; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009154:Mutation; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012737:Sex Factors
D000974:Antibodies, Antinuclear; D017452:Receptors, IgG; D008627:Mercuric Chloride