Specificity and cross-reactive idiotypes of anti-glomerular basement membrane autoantibodies in HgCl2-induced autoimmune glomerulonephritis.
Mercury-induced autoimmune glomerulonephritis in the Brown-Norway (BN) rat is characterized by the successive appearance of linear and granular glomerular IgG deposits. Anti-laminin autoantibodies represent the major part of the anti-glomerular basement membrane (GBM) antibodies produced in this model. Fusions were performed in this model and four anti-GBM monoclonal antibodies (mAb) were obtained. Three of them were laminin specific. Using rabbit anti-idiotype antibodies, cross-reactive idiotypes (CRId) were characterized on anti-laminin antibodies. They were expressed on the three anti-laminin mAb, on kidney-eluted and circulating anti-laminin antibodies. CRId-bearing immunoglobulins were detected transiently in the circulation and paralleled the anti-laminin antibody activity. By immunofluorescence studies on kidney cryostat sections two different CRId were defined. One was localized close to the antigen-combining site since it was not revealed on kidney-bound antibodies, in contrast with the second CRId. This latter CRId was also found deposited in a typical linear pattern in the early phase of the disease and in a granular pattern in the late phase, demonstrating that these CRId are components of immune deposits. Taken together, these results suggest that in this model of T-dependent polyclonal B cell activation, restricted sets of V genes encode for at least a part of the anti-GBM autoantibodies.
Unité 28, Institut National de la Santé et de la Recherche Médicale, Hôpital Broussais, Paris, France.
J C
JC
Guéry
E
E
Druet
D
D
Glotz
F
F
Hirsch
C
C
Mandet
E
E
De Heer
P
P
Druet
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology*; D003429:Cross Reactions; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology*; D007797:Laminin / Q000276:immunology*; D008627:Mercuric Chloride; D051381:Rats; D011914:Rats, Inbred BN
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007130:Immunoglobulin Idiotypes; D007797:Laminin; D008627:Mercuric Chloride