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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Sep;85(3):379–385. doi: 10.1111/j.1365-2249.1991.tb05735.x

IgG human monoclonal anti-DNA autoantibodies from patients with systemic lupus erythematosus.

T H Winkler 1, S Jahn 1, J R Kalden 1
PMCID: PMC1535604  PMID: 1893617

Abstract

We describe the production of six mouse-human heterohybridomas secreting human IgG anti-dsDNA antibodies derived from patients with systemic lupus erythematosus (SLE). Peripheral blood cells used for fusion experiments were from patients who were shown to have high numbers of anti-DNA secreting B cells in the peripheral blood. All monoclonal antibodies bind to dsDNA in ELISA systems, five are reactive with Crithidia lucilae kinetoplasts and three precipitate dsDNA in the Farr assay. Inhibition studies revealed a remarkable specificity for certain polynucleotide structures. To our knowledge these are the first hybridomas described in the human system that secrete anti-dsDNA antibodies of the IgG class.

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Selected References

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  1. Aarden L. A., De Groot E. R., Lakmaker F. Immunology of DNA. V. Analysis of DNA/anti-DNA complexes. J Immunol Methods. 1976;13(3-4):241–252. doi: 10.1016/0022-1759(76)90071-5. [DOI] [PubMed] [Google Scholar]
  2. Aarden L. A., Lakmaker F., Feltkamp T. E. Immunology of DNA. I. The influence of reaction conditions on the Farr assay as used for the detection of anti-ds DNA. J Immunol Methods. 1976;10(1):27–37. doi: 10.1016/0022-1759(76)90004-1. [DOI] [PubMed] [Google Scholar]
  3. Aarden L. A., de Groot E. R., Feltkamp T. E. Immunology of DNA. III. Crithidia luciliae, a simple substrate for the determination of anti-dsDNA with the immunofluorescence technique. Ann N Y Acad Sci. 1975 Jun 30;254:505–515. doi: 10.1111/j.1749-6632.1975.tb29197.x. [DOI] [PubMed] [Google Scholar]
  4. Andersson J., Melchers F. The antibody repertoire of hybrid cell lines obtained by fusion of X63-AG8 myeloma cells with mitogen-activated B-cell blasts. Curr Top Microbiol Immunol. 1978;81:130–139. doi: 10.1007/978-3-642-67448-8_19. [DOI] [PubMed] [Google Scholar]
  5. Ebling F., Hahn B. H. Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus. Comparison of antibodies in serum and renal eluates. Arthritis Rheum. 1980 Apr;23(4):392–403. doi: 10.1002/art.1780230402. [DOI] [PubMed] [Google Scholar]
  6. Friguet B., Chaffotte A. F., Djavadi-Ohaniance L., Goldberg M. E. Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay. J Immunol Methods. 1985 Mar 18;77(2):305–319. doi: 10.1016/0022-1759(85)90044-4. [DOI] [PubMed] [Google Scholar]
  7. Hoch S., Schwaber J. Specificity analysis of human anti-DNA antibodies. J Immunol. 1986 Feb 1;136(3):892–897. [PubMed] [Google Scholar]
  8. Ishigatsubo Y., Sakamoto H., Hagiwara E., Aoki A., Shirai A., Tani K., Okubo T., Klinman D. M. Quantitation of autoantibody-secreting B cells in systemic lupus erythematosus. Autoimmunity. 1989;5(1-2):71–78. doi: 10.3109/08916938909029144. [DOI] [PubMed] [Google Scholar]
  9. Kiessig S. T., Jahn S., Hiepe F., Volk H. D., Fietze E., Zugehör M., Porstmann T., von Baehr R. Multireactive human monoclonal antibodies. Allerg Immunol (Leipz) 1990;36(3):163–177. [PubMed] [Google Scholar]
  10. Kofler R., Noonan D. J., Strohal R., Balderas R. S., Møller N. P., Dixon F. J., Theofilopoulos A. N. Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes. Eur J Immunol. 1987 Jan;17(1):91–95. doi: 10.1002/eji.1830170116. [DOI] [PubMed] [Google Scholar]
  11. Lafer E. M., Rauch J., Andrzejewski C., Jr, Mudd D., Furie B., Furie B., Schwartz R. S., Stollar B. D. Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids. J Exp Med. 1981 Apr 1;153(4):897–909. doi: 10.1084/jem.153.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Rauch J., Massicotte H., Tannenbaum H. Hybridoma anti-DNA autoantibodies from patients with rheumatoid arthritis and systemic lupus erythematosus demonstrate similar nucleic acid binding characteristics. J Immunol. 1985 Jan;134(1):180–186. [PubMed] [Google Scholar]
  14. Rothfield N. F., Stollar B. D. The relation of immunoglobulin class, pattern of anti-nuclear antibody, and complement-fixing antibodies to DNA in sera from patients with systemic lupus erythematosus. J Clin Invest. 1967 Nov;46(11):1785–1794. doi: 10.1172/JCI105669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sedgwick J. D., Holt P. G. A solid-phase immunoenzymatic technique for the enumeration of specific antibody-secreting cells. J Immunol Methods. 1983 Feb 25;57(1-3):301–309. doi: 10.1016/0022-1759(83)90091-1. [DOI] [PubMed] [Google Scholar]
  16. Seigneurin J. M., Guilbert B., Bourgeat M. J., Avrameas S. Polyspecific natural antibodies and autoantibodies secreted by human lymphocytes immortalized with Epstein-Barr virus. Blood. 1988 Mar;71(3):581–585. [PubMed] [Google Scholar]
  17. Shlomchik M., Mascelli M., Shan H., Radic M. Z., Pisetsky D., Marshak-Rothstein A., Weigert M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–292. doi: 10.1084/jem.171.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shoenfeld Y., Rauch J., Massicotte H., Datta S. K., André-Schwartz J., Stollar B. D., Schwartz R. S. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med. 1983 Feb 24;308(8):414–420. doi: 10.1056/NEJM198302243080802. [DOI] [PubMed] [Google Scholar]
  19. Smeenk R. J., Brinkman K., van den Brink H. G., Westgeest A. A. Reaction patterns of monoclonal antibodies to DNA. J Immunol. 1988 Jun 1;140(11):3786–3792. [PubMed] [Google Scholar]
  20. Smeenk R. J., Lucassen W. A., Swaak T. J. Is anticardiolipin activity a cross-reaction of anti-DNA or a separate entity? Arthritis Rheum. 1987 Jun;30(6):607–617. doi: 10.1002/art.1780300602. [DOI] [PubMed] [Google Scholar]
  21. Stollar B. D., Zon G., Pastor R. W. A recognition site on synthetic helical oligonucleotides for monoclonal anti-native DNA autoantibody. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4469–4473. doi: 10.1073/pnas.83.12.4469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Swaak A. J., Aarden L. A., Statius van Eps L. W., Feltkamp T. E. Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Arthritis Rheum. 1979 Mar;22(3):226–235. doi: 10.1002/art.1780220304. [DOI] [PubMed] [Google Scholar]
  23. Tan E. M. Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol. 1982;33:167–240. doi: 10.1016/s0065-2776(08)60836-6. [DOI] [PubMed] [Google Scholar]
  24. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  25. Ternynck T., Avrameas S. Murine natural monoclonal autoantibodies: a study of their polyspecificities and their affinities. Immunol Rev. 1986 Dec;94:99–112. doi: 10.1111/j.1600-065x.1986.tb01166.x. [DOI] [PubMed] [Google Scholar]
  26. Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]
  27. Unger B., Klock G., Hillen W. Nucleotide sequence of the repressor gene of the RA1 tetracycline resistance determinant: structural and functional comparison with three related Tet repressor genes. Nucleic Acids Res. 1984 Oct 25;12(20):7693–7703. doi: 10.1093/nar/12.20.7693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Winkler T. H., Henschel T. A., Kalies I., Baenkler H. W., Skvaril F., Kalden J. R. Constant isotype pattern of anti-dsDNA antibodies in patients with systemic lupus erythematosus. Clin Exp Immunol. 1988 Jun;72(3):434–439. [PMC free article] [PubMed] [Google Scholar]

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