Mercury induces polyclonal B cell activation, autoantibody production and renal immune complex deposits in young (NZB x NZW)F1 hybrids.
It is well established that in susceptible mouse strains, chronic treatment with subtoxic doses of mercuric chloride (HgCl2) induces a systemic autoimmune disease, which is characterized by increased serum levels of IgG1 and IgE antibodies, by the production of anti-nucleolar antibodies and by the development of immune complex-mediated glomerulonephritis. Susceptibility to mercury is partly under the control of major histocompatibility complex genes. To study the susceptibility to mercury further, we investigated the in vivo effects of mercury in young autoimmune disease prone (NZB x NZW)F1 (H-2d/z) mice prior to establishment of spontaneous autoimmune disease. Mercury-susceptible SJL (H-2s) mice and mercury low-responder BALB/c (H-2d) mice were used as positive and negative controls, respectively. In (NZB x NZW)F1 mice, treatment with mercury stimulated an intense antibody formation characterized by increased numbers of splenic IgG1 and IgG3 antibody-producing cells as well as by elevated serum IgE levels. Injection with mercury also induced an increased production of IgG1, IgG2b and IgE antibodies in SJL, but not in BALB/c mice. The mercury-induced IgG1 response in (NZB x NZW)F1 and SJL mice was found to be polyclonal and autoantibodies against double-stranded (ds)DNA, IgG, collagen, cardiolipin, phosphatidylethanolamine as well as antibodies against the hapten trinitrophenol were produced. In addition, SJL, but not (NZB x NZW)F1 or BALB/c mice, produced IgG1 anti-nucleolar antibodies after treatment with mercury. Further studies demonstrated that (NZB x NZW)F1 and SJL mice developed high titers of renal mesangial immune complex deposits containing IgG1 antibodies 3 weeks after injection with mercury. Thus, a mouse strain genetically prone to develop spontaneous autoimmune diseases is highly susceptible to mercury-induced immunopathological alterations.
al-Balaghi
S
S
Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Möller
E
E
Möller
G
G
Abedi-Valugerdi
M
M
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000096:biosynthesis* / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D002466:Cell Nucleolus / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D007105:Immune Complex Diseases / Q000139:chemically induced* / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007668:Kidney / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008627:Mercuric Chloride / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D013045:Species Specificity
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D008627:Mercuric Chloride