GLOMERULOPATHY INDUCED BY A SINGLE MONOCLONAL AUTOANTIBODY AGAINST GP330

Monoclonal autoantibodies were obtained from Lewis rats with active He ymann nephritis. Two cloned rat/mouse hybridomas, 3D9B and 5B8C, that secreted rat IgG2a autoantibodies were selected for their ability to r eact with gp330 in ELISA and propagated further. Their specificity was confirmed by immunoprecipitation of crude antigens from a yolk sac ca rcinoma cell line expressing gp330, The size of the precipitated molec ule was identical to that immunoprecipitated by previously described a nti-gp330 antibodies. Indirect immune-electron microscopy showed that 3D9B exclusively stained the intermicrovillous areas of the tubular br ush border membrane, while 5B8C stained the full tubular microvillous membrane and the glomerular epithelial coated pits. Passive transfer o f 3D9B did not induce Ig deposits or functional renal damage within 7 days. However, injection of 5B8C caused granular glomerular deposits w ithin 1 h, subepithelial immune aggregates within 6 days and antibody deposition on the brush border within 7 days. Only ascites production of clone 5B8C in rats, but not in mice, caused subepithelial immune de posits and abnormal proteinuria. This study shows that a single monocl onal autoantibody to gp330 is able to induce a mild form of Heymann ne phritis.