Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1982 May 1;155(5):1385–1399. doi: 10.1084/jem.155.5.1385

Deposition of idiotype-anti-idiotype immune complexes in renal glomeruli after polyclonal B cell activation

PMCID: PMC2186687  PMID: 7040591

Abstract

We investigated the possible role of idiotypic interactions in the pathogenesis of the glomerular lesions observed in mice undergoing polyclonal B cell activation. BALB/c mice were studied for the presence of renal deposits of T15 idiotype-anti-T15 idiotype-immune complexes (IC) after injection of bacterial lipopolysaccharides (LPS). The T15 idiotype is the major idiotype of BALB/c mice anti-phosphorylcholine (PC) antibodies, which are cross-reactive with the idiotype of the TEPC- 15 myeloma protein. This model was used because T15 idiotype-anti-T15 idiotype IC have been detected in the circulation of BALB/c mice after polyclonal B cell activation. First, an idiotype-specific immunofluorescence technique allowed us to detect T15 idiotype-bearing immunoglobulins in glomeruli from day 6 to day 28 after LPS injection. Second, fluorescein isothiocyanate-conjugated TEPC-15 myeloma protein was found to localize in the glomeruli after in vivo injection 18 d after LPS administration. This renal localization was shown to be idiotype-specific and could be quantified in a trace-labeling experiment. Third, kidney-deposited immunoglobulins of mice injected with LPS were eluted, radiolabeled, and analyzed by radioimmunoassay. Both T15 idiotype-bearing immunoglobulins and anti-T15 idiotype antibodies were detected in the eluates, providing further evidence for a renal deposition of T15 idiotype-anti-T15 idiotype IC. Polyclonal B cell activation is likely to result in a simultaneous triggering of many idiotypic clones and of corresponding anti-idiotypic clones represented in the B cell repertoire. This could lead to the formation of a variety of idiotype-anti-idiotype IC that could participate in the development of glomerular lesions.

Full Text

The Full Text of this article is available as a PDF (2.2 MB).

Selected References

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

  1. Abdou N. I., Wall H., Lindsley H. B., Halsey J. F., Suzuki T. Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus. J Clin Invest. 1981 May;67(5):1297–1304. doi: 10.1172/JCI110158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agnello V., Koffler D., Eisenberg J. W., Winchester R. J., Kundel H. G. C1g precipitins in the sera of patients with systemic lupus erythematosus and other hypocomplementemic states: characterization of high and low molecular weight types. J Exp Med. 1971 Sep 1;134(3 Pt 2):228s–241s. [PubMed] [Google Scholar]
  3. Berek C., Schreier M. H., Sidman C. L., Jaton J. C., Kocher H. P., Cosenza H. Phosphorylcholine-binding hybridoma proteins of normal and idiotypically suppressed BALB/c mice I. Characterization and idiotypic analysis. Eur J Immunol. 1980 Apr;10(4):258–263. doi: 10.1002/eji.1830100407. [DOI] [PubMed] [Google Scholar]
  4. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Border W. A. Immune complex detection in glomerular diseases. Nephron. 1979;24(3):105–113. doi: 10.1159/000181698. [DOI] [PubMed] [Google Scholar]
  6. Casali P., Bossus A., Carpentier N. A., Lambert P. H. Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test. A comparative study with 125I-labelled Clq binding and Raji-cell RIA tests. Clin Exp Immunol. 1977 Aug;29(2):342–354. [PMC free article] [PubMed] [Google Scholar]
  7. Chesebro B., Metzger H. Affinity labeling of a phosphorylcholine binding mouse myeloma protein. Biochemistry. 1972 Feb 29;11(5):766–771. doi: 10.1021/bi00755a014. [DOI] [PubMed] [Google Scholar]
  8. Claflin J. L., Lieberman R., Davie J. M. Clonal nature of the immune response to phosphorylcholine. II. Idiotypic specificity and binding characteristics of anti-phosphorylcholine antibodies. J Immunol. 1974 May;112(5):1747–1756. [PubMed] [Google Scholar]
  9. Couser W. G., Salant D. J. In situ immune complex formation and glomerular injury. Kidney Int. 1980 Jan;17(1):1–13. doi: 10.1038/ki.1980.1. [DOI] [PubMed] [Google Scholar]
  10. Couser W. G. What are circulating immune complexes doing in glomerulonephritis? N Engl J Med. 1981 May 14;304(20):1230–1232. doi: 10.1056/NEJM198105143042011. [DOI] [PubMed] [Google Scholar]
  11. Cuatrecasas P. Protein purification by affinity chromatography. Derivatizations of agarose and polyacrylamide beads. J Biol Chem. 1970 Jun;245(12):3059–3065. [PubMed] [Google Scholar]
  12. Dixon F. J. The pathogenesis of glomerulonephritis. Am J Med. 1968 Apr;44(4):493–498. doi: 10.1016/0002-9343(68)90050-8. [DOI] [PubMed] [Google Scholar]
  13. Dresser D. W. Most IgM-producing cells in the mouse secrete auto-antibodies (rheumatoid factor). Nature. 1978 Aug 3;274(5670):480–483. doi: 10.1038/274480a0. [DOI] [PubMed] [Google Scholar]
  14. Fournié G. J., Lambert P. H., Meischer P. A. Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1189–1206. doi: 10.1084/jem.140.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Geltner D., Franklin E. C., Frangione B. Antiidiotypic activity in the IgM fractions of mixed cryoglobulins. J Immunol. 1980 Oct;125(4):1530–1535. [PubMed] [Google Scholar]
  16. Goetzl E. J., Metzger H. Affinity labeling of a mouse myeloma protein which binds nitrophenyl ligands. Kinetics of labeling and isolation of a labeled peptide. Biochemistry. 1970 Mar 3;9(5):1267–1278. doi: 10.1021/bi00807a031. [DOI] [PubMed] [Google Scholar]
  17. Greenwood B. M. Possible role of a B-cell mitogen in hypergammaglobulinaemia in malaria and trypanosomiasis. Lancet. 1974 Mar 16;1(7855):435–436. doi: 10.1016/s0140-6736(74)92386-1. [DOI] [PubMed] [Google Scholar]
  18. Izui S., Lambert P. H., Fournié G. J., Türler H., Miescher P. A. Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes. J Exp Med. 1977 May 1;145(5):1115–1130. doi: 10.1084/jem.145.5.1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Izui S., Lambert P. H., Miescher P. A. In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus. J Exp Med. 1976 Aug 1;144(2):428–443. doi: 10.1084/jem.144.2.428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Izui S., McConahey P. J., Dixon F. J. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed] [Google Scholar]
  21. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  22. Kobayakawa T., Louis J., Izui S., Lambert P. H. Autoimmune response to DNA, red blood cells, and thymocyte antigens in association with polyclonal antibody synthesis during experimental African trypanosomiasis. J Immunol. 1979 Jan;122(1):296–301. [PubMed] [Google Scholar]
  23. Lambert P. H., Dixon F. J. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968 Mar 1;127(3):507–522. doi: 10.1084/jem.127.3.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Maire M. A., Barnet M., Lambert P. H. Purification of bovine conglutinin using pepsin digestion. Mol Immunol. 1981 Feb;18(2):85–89. doi: 10.1016/0161-5890(81)90073-0. [DOI] [PubMed] [Google Scholar]
  25. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Potter M. Immunoglobulin-producing tumors and myeloma proteins of mice. Physiol Rev. 1972 Jul;52(3):631–719. doi: 10.1152/physrev.1972.52.3.631. [DOI] [PubMed] [Google Scholar]
  28. Rose L. M., Goldman M., Lambert P. H. Simultaneous induction of an idiotype, corresponding anti-idiotypic antibodies, and immune complexes during African trypanosomiasis in mice. J Immunol. 1982 Jan;128(1):79–85. [PubMed] [Google Scholar]
  29. Rose L. M., Lambert P. H. The natural occurence of circulating idiotype--anti-idiotype complexes during a secondary immune response to phosphorylcholine. Clin Immunol Immunopathol. 1980 Mar;15(3):481–492. doi: 10.1016/0090-1229(80)90060-4. [DOI] [PubMed] [Google Scholar]
  30. Wilson C. B., Dixon F. J. Antigen quantitation in experimental immune complex glomerulonephritis. I. Acute serum sickness. J Immunol. 1970 Aug;105(2):279–290. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES