Evidence for a role of antilaminin-producing B cell clones that escape tolerance in the pathogenesis of HgCl2-induced membranous glomerulopathy.
In Brown-Norway rats HgCl2 induces an autoimmune disease due to a T-dependent B cell polyclonal activation. This disease is marked by the production of numerous antibodies including antiglomerular basement membrane (GBM) antibodies. Rats exhibit a biphasic glomerulopathy with heavy proteinuria. Initially anti-GBM antibodies are found linearly deposited; they precede the appearance of membranous glomerulopathy. Rats recover spontaneously even if HgCl2 injections are pursued, but mechanisms at play are unclear. We have assessed the effects of transplanting the spleen from a BN rat, either at the acme of the disease or at the time of convalescence, into naive BN rats, some of which were then injected with HgCl2. Transplantation of a spleen from HgCl2-injected rats at the acme of the disease dramatically protects BN rats from all the manifestations of the mercury disease. BN rats transplanted with a spleen from HgCl2-injected rats at the time of convalescence only exhibited a typical membranous glomerulopathy with heavy proteinuria but without circulating anti-GBM antibodies. Antilaminin antibodies were eluted from the glomeruli. This study shows that spleen cells from HgCl2-injected rats are able to confer tolerance to HgCl2-induced autoimmunity. It also shows that some B cell clones escape this tolerance. Finally, this study strongly suggests that membranous glomerulopathy, responsible for proteinuria in this model, is related to the presence of antilaminin antibodies.
Laboratoire de recherches chirurgicales, Hôpital Cochin, Paris, France.
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Icard
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Pelletier
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Vial
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Mandet
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Pasquier
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Michel
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Druet
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000276:immunology*; D007108:Immune Tolerance; D007678:Kidney Glomerulus / Q000276:immunology; D007797:Laminin / Q000276:immunology*; D008297:Male; D008627:Mercuric Chloride; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000276:immunology / Q000637:transplantation
D001323:Autoantibodies; D007797:Laminin; D008627:Mercuric Chloride