Specificity and cross‐reactive idiotypes of anti‐glomerular basement membrane autoantibodies in HgCl2‐induced autoimmune glomerulonephritis

Abstract

Murcury‐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.