A MONOCLONAL-ANTIBODY TO BRUSH-BORDER AND PASSIVE HEYMANN NEPHRITIS

Abstract

An IgG2a monoclonal antibody (MoAb) reacting with the brush border of the renal proximal tubule and glomerular capillary wall was produced by fusion of NS1 [mouse] myeloma cells with spleen cells from BALB/c mice immunized with renal brush border preparations from rat kidney cortex. This antibody reacts with a 90,000 MW protein which can be isolated by immunoprecipitation of radiolabeled brush border or glomerular preparations and localized on these structures by immunoperoxidase EM, demonstrating the presence of common antigenic determinants. Survey of various organs showed that the MoAb reacted with the brush border of the gut, but also with antigens associated with the distal vascular system. In the liver antigenic determinants were located along the sinusoid walls but mainly on bile canaliculi. Specific glomerular binding could be demonstrated in vivo by immunofluorescence after an i.v. injection of 2 mg of antibody or by paired label methodology using tracer amounts. Kinetics were dramatically different from those observed in classical passive Heymann nephritis since glomerular binding was transient during the 1st hours after injection. Binding was also found in tubular structures, as well as in lung, liver, spleen and heart. The results identify a well defined antigen-antibody system responsible for the formation of transient extramembranous glomerular deposits and may be relevant to some human cases of glomerulonephritis. They may also provide new models to study glomerular and tubular transfer of membrane bound antibodies.