title: Spontaneous downregulation of antibody/autoantibody synthesis in susceptible mice upon chronic exposure to mercuric chloride is not owing to a general immunosuppression.
abstract: Administration of mercuric chloride into susceptible rats and mice induces a systemic autoimmune disease, which is characterized by a T-cell-dependent polyclonal B-cell activation, an increase in serum levels of immunoglobulin (Ig)G1 and IgE, production of antibodies of different specificities and development of renal IgG deposits. A peculiar feature of mercury-induced autoimmunity is that the polyclonal B-cell activation spontaneously disappears in spite of continuous injection of mercury. The exact mechanism(s) for autoregulation of mercury-induced autoimmunity is not well understood. In the present study, we analysed the regulation of mercury-induced immune/autoimmune responses in mice and tested whether spontaneous downregulation of these responses is owing to a general immunosuppression. Mercury-susceptible [SJL (H-2s)] and -resistant [DBA/2 (H-2d)] mice were injected with mercury for 4, 10, 15 and 17 weeks. Immune/autoimmune responses were monitored in these mice. Thereafter, mercury-injected mice for 17 weeks were further immunized with horse red blood cells (HRBC) to study whether the subsequent humoral immune response to a foreign antigen is suppressed. We found that except for IgG1 anti-nucleolar antibody production and renal IgG1 deposition, other characteristics of mercury-induced autoimmunity were downregulated in SJL (H-2s) mice after chronic treatment with mercury. However, these mice did not show any reduction in the number of splenic antibody-secreting cells and/or in serum titres of specific IgM, IgG1 and IgG2a anti-HRBC antibodies in response to HRBC as compared with naïve mice. Similarly, in mercury-resistant DBA/2 (H-2d) mice, chronic treatment with mercury did not either suppress specific antibody responses against HRBC. Our findings show that the autoregulation of mercury-induced immune/autoimmune responses observed after chronic treatment with mercury is not owing to a general immunosuppression.
authors.affiliation: Department of Immunology, The Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Roether
authors.forename: H
authors.initials: H
authors.lastname: Rabbani
authors.forename: H
authors.initials: H
authors.lastname: Mellstedt
authors.forename: M
authors.initials: M
authors.lastname: Abedi-Valugerdi
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000235:genetics; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006736:Horses; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D007371:Interferon-gamma