Characteristics of polyreactive and monospecific IgG anti-laminin autoantibodies in the rat mercury model.
Brown-Norway (BN) rats injected with HgCl2 produce anti-laminin antibodies responsible for an autoimmune glomerulonephritis. The properties of three IgG1 monoclonal antibodies (mAb) previously obtained in this model, and of immunoglobulins eluted from kidneys of diseased rats, were compared in the present study. Two mAb (Hg15 and Hg16) recognized laminin only, while the third one (Hg17) was polyreactive, as were some of the kidney-eluted immunoglobulins; they reacted with laminin and with several other antigens including 2,4,6-trinitrophenyl (TNP). The Hg17 mAb and kidney-eluted polyreactive antibodies were affinity purified using a TNP-bovine serum albumin (BSA) column; their affinity for TNP was high (2 x 10(-8)M, and 1 x 10(-8)M, respectively) but less than that of a TNP-specific (LO-DNP-2) mAb (2 x 10(-11) M). The Hg17 mAb and kidney-eluted antibodies reacted more effectively with TNP28-BSA than with TNP8.5-BSA, while the TNP-specific mAb reacted equally well with both conjugates. The Hg17 mAb was the most cationic (pI: 7) of the anti-laminin mAb and this was even more evident when F(ab')2 fragments were studied (pI: 8.2). The polyreactive kidney-eluted immunoglobulins that bound TNP were also more cationic (pI: 7.4-9.3) than the fraction that did not recognize TNP (pI: 5.8-8.6). The anti-laminin mAb bound in vivo to the glomerular basement membrane, but only the Hg17 mAb could be eluted with DNP alone. This study shows that polyreactive anti-laminin antibodies are produced during this autoimmune disease, and indicates that they may have pathogenic potential.
INSERM U28, Hôpital Broussais, Paris, France.
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Druet
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Guery
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Ayed
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Guilbert
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Avrameas
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Druet
D000818:Animals; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000276:immunology*; D005921:Glomerulonephritis / Q000276:immunology*; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology*; D007525:Isoelectric Focusing; D007668:Kidney / Q000276:immunology*; D007797:Laminin / Q000276:immunology*; D008627:Mercuric Chloride; D051381:Rats; D011914:Rats, Inbred BN
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D007797:Laminin; D008627:Mercuric Chloride