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Establishment of monoclonal antibodies which possess the same characteristics as the naturally occurring thymocytotoxic autoantibodies (NTA)

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Summary

Autoantibody-secreting hybrid cell lines were obtained by fusion of spleen cells from unimmunized (NZB×NZW) F1 mice with the HAT-sensitive mouse myeloma cell line SP2/0-Ag14. Eight hybridoma cell lines producing autoantibodies to mouse thymocytes were cloned and the resultant antibodies were partially characterized. All eight monoclonal antibodies lysed mouse thymocytes in the presence of rabbit complement. The anti-thymocyte cytotoxic antibody activities were absorbed with thymocytes, lymph node cells, unfractionated spleen cells, and splenic T cells; but not with bone marrow cells, splenic B cells, or homogenates of mouse kidney, liver, or striated muscle cells. In addition, the cytotoxic activities of culture supernatants from seven of the eight hybrid clones were absorbed with mouse brain tissue homogenates. Isotyping of the monoclonal antibodies revealed that five were IgM and three were IgG2a. Mouse thymocytes sensitized with each of the eight monoclonal antibodies in vitro became highly susceptible to phagocytosis by syngeneic macrophages. The monoclonal antithymocyte antibodies, thus, appear to be similar to the naturally occurring, (NZB×NZW) F1 thymocytotoxic autoantibodies (NTA) described by Shirai et al. [20–23].

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References

  1. Talal N, Steinberg AD (1974) Pathogenesis of autoimmunity in New Zealand Black mice. Curr Top Microbiol Immunol 64:79–103

    Google Scholar 

  2. Allison AC, Denman AM, Barnes RD (1971) Cooperating and controlling functions of thymus-derived lymphocytes in relation to autoimmunity. Lancet II:135–140

    Google Scholar 

  3. Barthold DR, Kysela S, Steinberg AD (1974) Decline in suppressor T cell with age in female NZB mice. J Immunol 112:9–16

    Google Scholar 

  4. Steinberg AD, Gerber N, Morton R, Gershwin M, Goodman D, Chused TM, Hardin JA, Barthold DR (1975) Loss of suppressor T cells in the pathogenesis of autoimmunity. Signhal S, Sinclair NSC (eds) Suppressor cells in immunity. University of Western Ontario, London, Canada, pp 174–180

    Google Scholar 

  5. Krakauer RS, Waldmann TA, Strober W (1976) Loss of suppressor T cells in adult NZB/NZW mice. J Exp Med 144:662–673

    Google Scholar 

  6. Roubinian JR, Papoian R, Talal N (1977) Effects of neonatal thymectomy and splenectomy on survival regulation of auto-antibody formation in (NZB×NZW) F1 mice. J Immunol 118:1524–1529

    Google Scholar 

  7. Sawada S, Talal N (1979) Characteristics of in vitro production of antibodies to DNA in normal and autoimmune mice. J Immunol 122:2309–2313

    Google Scholar 

  8. DeHeer DH, Edgington TS (1977) Evidence for a B lymphocyte defect underlying the anti-X anti-erythrocyte autoantibody response of NZB mice. J Immunol 118:1858–1863

    Google Scholar 

  9. Cohen PL, Ziff M (1977) Abnormal polyclonal B cell activation in NZB/NZW F1 mice. J Immunol 119:1534–1537

    Google Scholar 

  10. Cohen P, Ziff M, Vitetta ES (1978) Characterization of a B cell defect in the NZB mouse manifested by an increased ratio of surface IgM to IgD. J Immunol 121:973–977

    Google Scholar 

  11. Steinberg AD, Huston DP, Taurog JK, Cowdery JW, Ravech ES (1981) The cellular and genetic basis of murine lupus. Immunol Rev 55:121–153

    Google Scholar 

  12. Gershwin ME, Castles JJ, Erickson K, Ahmed A (1979) Studies of congenitally immunologic mutant New Zealand mice. II. Absence of T cell progenitor populations and B cell defects of congenitally athymic (nude) New Zealand Black (NZB) mice. J Immunol 122:2020–2025

    Google Scholar 

  13. Manny NS, Datta SK, Schwartz RS (1979) Synthesis of IgM by cells of NZB and SWR mice and their crosses. J Immunol 122:1220–1227

    Google Scholar 

  14. Chused T, Moutsopoulos H, Charrow S, Hansen C (1979) Evidence of a primary B-lymphocyte abnormality in NZB mice. In: Cooper M, Mosier DE, Scher I, Vitetta ES (eds) B lymphocytes in the immune response. Elsevier/North-Holland, New York Amsterdam Oxford, pp 363

    Google Scholar 

  15. Izui S, McConahey PJ, Dixon FJ (1978) Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol 121:2213–2219

    Google Scholar 

  16. Primi D, Hammarstrom L, Smith CIE, Moller G (1977) Characterization of self-reactive B cells by polyclonal B-cell activators. J Exp Med 145:2130

    Google Scholar 

  17. Izui S, Kobayakawa T, Zryd MJ, Louis J, Lambert PH (1977) Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice. II. Correlation between anti-DNA induction and polyclonal antibody formation by various polyclonal B lymphocyte activators. J Immunol 119:2157–2162

    Google Scholar 

  18. Cunningham AJ (1975) Active suppressor mechanism maintaining tolerance to some self components. Nature 254:143–144

    Google Scholar 

  19. Izui S, Kobayakawa T, Louis J, Lambert PH (1979) Induction of thymocytotoxic autoantibodies after injection of bacterial lipopolysaccharides in mice. Eur J Immunol 9:338–341

    Google Scholar 

  20. Shirai T, Mellors RC (1971) Natural thymocytotoxic autoantibody and reactive antigen in New Zealand black and other mice. Proc Natl Acad Sci USA 68:1412–1415

    Google Scholar 

  21. Shirai T, Mellors RC (1972) Natural cytotoxic autoantibody against thymocytes in NZB mice. Clin Exp Immunol 12:133–152

    Google Scholar 

  22. Shirai T, Yoshiki T, Mellors RC (1972) Thymus dependence of cells in peripheral lymphoid tissues and in the circulation sensitive to natural thymocytotoxic autoantibody in NZB mice. J Immunol 109:32–37

    Google Scholar 

  23. Shirai T, Yoshiki T, Mellors RC (1972) Age-decrease of cells sensitive to an autoantibody specific for thymocytes and thymus-dependent lymphocytes in NZB mice. Clin Exp Immunol 12:455–464

    Google Scholar 

  24. Shirai T, Yoshiki T, Mellors RC (1973) Effects of natural thymocytotoxic autoantibody of NZB mice and of specifically prepared antilymphocyte serum on the tissue distribution of 51Cr-labeled lymphocytes. J Immunol 110:517–523

    Google Scholar 

  25. Shirai T, Hayakawa K, Okumura K, Tada T (1978) Differential cytotoxic effect of natural thymocytotoxic autoantibody of NZB mice on functional subsets of T cells. J Immunol 120:1924–1929

    Google Scholar 

  26. Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497

    Google Scholar 

  27. Hammerling GV, Hammerling V, Lemke H (1979) Isolation of twelve monoclonal antibodies against Ia and H-2 antigens. Serological characterization and reactivity with B and with B and T lymphocytes. Immunogenetics 8:433–445

    Google Scholar 

  28. Aihara Y, Todokoro I, Katoh K, Minami M, Okuda K (1983) T cell allotypic determinants encoded by genes linked to the immunoglobulin heavy chain locus. I. Establishment of monoclonal antibodies against allotypic determinants. J Immunol 130:2920–2925

    Google Scholar 

  29. Voller A, Bidwell D, Bartlett A (1980) Enzyme linked immunosorbent assay. In: Rose NR, Friedman H (eds) Manual of clinical immunology, 2nd edn. American Society of Microbiology, Washington, DC, pp 359–371

    Google Scholar 

  30. Crowle AJ (1980) Precipitin and microprecitin reactions in fluid medium and in gels (1980) In: Rose NR, Friedman H (eds) Manual of clinical immunology, 2nd edn. American Society of Microbiology, Washington, DC, pp 3–14

    Google Scholar 

  31. Takahashi T, Old LJ, Boyse EA (1970) Surface alloantigens of plasma cells. J Exp Med 131:1325–1341

    Google Scholar 

  32. Handwerger BS, Schwartz RH (1974) Separation of murine lymphoid cells using nylon wool columns: recovery of the B cell-enriched population. Transplantation 18:544–548

    Google Scholar 

  33. Reif AE, Allen (1964) The AKR thymic antigen and its distribution in leukemias and nervous tissues. J Exp Med 120:413–433

    Google Scholar 

  34. Klassen LW, Krakauer RS, Steinberg AD (1977) Selective loss of suppressor cell function in New Zealand mice induced by NTA. J Immunol 119:830–836

    Google Scholar 

  35. Hoffman AA, Harbeck RF (1979) Immunoregulation in New Zealand mice. I. Failure of the transfer of syngeneic spleen or thymus cells to influence the natural disease in New Zealand mice. Arthritis Rheum 22:412–418

    Google Scholar 

  36. Theofilopoulos AN, Shawler DL, Eisenberg RA, Dixon FJ (1980) Specific immunoglobulin-secreting cells and their regulation in autoimmune mice. J Exp Med 151:446–466

    Google Scholar 

  37. Nakanishi A, Imai Y, Nakano T, Owawa T (1982) Induction of autoimmune phenomena in normal mice treated with natural thymocytotoxic antibody. J Immunol 128:2137–2141

    Google Scholar 

  38. Golub ES (1971) Brain-associated θ antigen: reactivity of rabbit anti-mouse brain with mouse lymphoid cells. Cell Immunol 2:353–361

    Google Scholar 

  39. Winfield JB, Winchester RJ, Wernet P, Fu SM, Kunkel HG (1975) Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus. Arthritis Rheum 18:1–8

    Google Scholar 

  40. Lies RB, Messner RP, Williams RC Jr (1973) Relative T-cell specificity of lymphotoxins form patients with systemic lupus erythematosus. Arthritis Rheum 16:369–375

    Google Scholar 

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Tani, K., Sakamoto, H., Katoh, K. et al. Establishment of monoclonal antibodies which possess the same characteristics as the naturally occurring thymocytotoxic autoantibodies (NTA). Rheumatol Int 6, 19–24 (1986). https://doi.org/10.1007/BF00270660

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  • DOI: https://doi.org/10.1007/BF00270660

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