Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1984 Feb;55(2):319–332.

A monoclonal antibody to brush border and passive Heymann nephritis.

P Ronco, L Allegri, C Melcion, E Pirotsky, M D Appay, J Bariety, F Pontillon, P Verroust
PMCID: PMC1535820  PMID: 6365376

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 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 mol. wt protein which can be isolated by immunoprecipitation of radiolabelled brush border or glomerular preparations and localized on these structures by immunoperoxidase electron microscopy, thus 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 intravenous injection of 2 mg of antibody or by paired label methodology using tracer amounts. Kinetics however were dramatically different from those observed in classical passive Heymann nephritis since glomerular binding was transient during the first hours after injection. Binding was also found in tubular structures, as well as in lung, liver, spleen and heart. These 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.

Full text

PDF
319

Images in this article

324Fig. 3
on p.324
324Fig. 4
on p.324
322Fig. 1
on p.322
323Fig. 2
on p.323
325Fig. 5
on p.325
325Fig. 6
on p.325
327Fig. 8
on p.327

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avrameas S., Ternynck T. Peroxidase labelled antibody and Fab conjugates with enhanced intracellular penetration. Immunochemistry. 1971 Dec;8(12):1175–1179. doi: 10.1016/0019-2791(71)90395-8. [DOI] [PubMed] [Google Scholar]
  2. Barabas A. Z., Lannigan R. Induction of an autologous immune-complex glomerulonephritis in the rat by intravenous injection of heterologous anti-rat kidney tubular antibody. I. Production of chronic progressive immune-complex glomerulonephritis. Br J Exp Pathol. 1974 Feb;55(1):47–55. [PMC free article] [PubMed] [Google Scholar]
  3. CLARK H. F., SHEPARD C. C. A DIALYSIS TECHNIQUE FOR PREPARING FLUORESCENT ANTIBODY. Virology. 1963 Aug;20:642–644. doi: 10.1016/0042-6822(63)90292-7. [DOI] [PubMed] [Google Scholar]
  4. Couser W. G., Steinmuller D. R., Stilmant M. M., Salant D. J., Lowenstein L. M. Experimental glomerulonephritis in the isolated perfused rat kidney. J Clin Invest. 1978 Dec;62(6):1275–1287. doi: 10.1172/JCI109248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Druet P., Bariéty J., Laliberté F., Bellon B., Belair M. F., Paing M. Distribution of heterologous antiperoxidase antibodies and their fragments in the superficial renal cortex of normal Wistar-Munich rat: an ultrastructural study. Lab Invest. 1978 Dec;39(6):623–631. [PubMed] [Google Scholar]
  6. Fleuren G. J., vd Lee R., Greben H. A., Van Damme B. J., Hoedemaeker P. J. Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. IV. Investigations into the pathogenesis of the model. Lab Invest. 1978 Apr;38(4):496–501. [PubMed] [Google Scholar]
  7. Fougereau M., Bourgois A., de Preval C., Rocca-Serra J., Schiff C. The complete sequence of the murine monoclonal immunoglobulin MOPC 173 (IgG2a): genetic implications. Ann Immunol (Paris) 1976 Sep-Oct;127(5):607–631. [PubMed] [Google Scholar]
  8. Glassock R. J., Edgington T. S., Watson J. I., Dixon F. J. Autologous immune complex nephritis induced with renal tubular antigen. II. The pathogenetic mechanism. J Exp Med. 1968 Mar 1;127(3):573–588. doi: 10.1084/jem.127.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HEYMANN W., HACKEL D. B., HARWOOD S., WILSON S. G., HUNTER J. L. Production of nephrotic syndrome in rats by Freund's adjuvants and rat kidney suspensions. Proc Soc Exp Biol Med. 1959 Apr;100(4):660–664. doi: 10.3181/00379727-100-24736. [DOI] [PubMed] [Google Scholar]
  10. Haakenstad A. O., Striker G. E., Mannik M. The glomerular deposition of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice. Lab Invest. 1976 Sep;35(3):293–301. [PubMed] [Google Scholar]
  11. Herbrink P., Van Bussel F. J., Warnaar S. O. The antigen spot test (AST): a highly sensitive assay for the detection of antibodies. J Immunol Methods. 1982;48(3):293–298. doi: 10.1016/0022-1759(82)90330-1. [DOI] [PubMed] [Google Scholar]
  12. KRAKOWER C. A., GREENSPON S. A. Localization of the nephrotoxic antigen within the isolated renal glomerulus. AMA Arch Pathol. 1951 Jun;51(6):629–639. [PubMed] [Google Scholar]
  13. Kerjaschki D., Farquhar M. G. Immunocytochemical localization of the Heymann nephritis antigen (GP330) in glomerular epithelial cells of normal Lewis rats. J Exp Med. 1983 Feb 1;157(2):667–686. doi: 10.1084/jem.157.2.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kerjaschki D., Farquhar M. G. The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5557–5561. doi: 10.1073/pnas.79.18.5557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
  16. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  17. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  18. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  19. Naruse T., Fukasawa T., Hirokawa N., Oike S., Miyakawa Y. The pathogenesis of experimental membranous glomerulonephritis induced with homologous nephritogenic tubular antigen. J Exp Med. 1976 Nov 2;144(5):1347–1362. doi: 10.1084/jem.144.5.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Naruse T., Fukasawa T., Miyakawa Y. Laboratory model of membranous glomerulonephritis in rats induced by pronase-digested homologous renal tubular epithelial antigen. Lab Invest. 1975 Aug;33(2):141–146. [PubMed] [Google Scholar]
  21. Neale T. J., Couser W. G., Salant D. J., Lowenstein L. M., Wilson C. B. Specific uptake of Heymann's nephritic kidney eluate by rat kidney: studies in vivo and in isolated perfused kidneys. Lab Invest. 1982 Apr;46(4):450–453. [PubMed] [Google Scholar]
  22. Neale T. J., Wilson C. B. Glomerular antigens in Heymann's nephritis: reactivity of eluted and circulating antibody. J Immunol. 1982 Jan;128(1):323–330. [PubMed] [Google Scholar]
  23. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  24. Phillips D. R., Agin P. P. Platelet membrane defects in Glanzmann's thrombasthenia. Evidence for decreased amounts of two major glycoproteins. J Clin Invest. 1977 Sep;60(3):535–545. doi: 10.1172/JCI108805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Salant D. J., Darby C., Couser W. G. Experimental membranous glomerulonephritis in rats. Quantitative studies of glomerular immune deposit formation in isolated glomeruli and whole animals. J Clin Invest. 1980 Jul;66(1):71–81. doi: 10.1172/JCI109837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Van Damme B. J., Fleuren G. J., Bakker W. W., Vernier R. L., Hoedemaeker P. J. Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. V. Fixed glomerular antigens in the pathogenesis of heterologous immune complex glomerulonephritis. Lab Invest. 1978 Apr;38(4):502–510. [PubMed] [Google Scholar]
  28. Wilfong R. F., Neville D. M., Jr The isolation of a brush border membrane fraction from rat kidney. J Biol Chem. 1970 Nov 25;245(22):6106–6112. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES