Journal of Clinical Immunology

, Volume 4, Issue 2, pp 124–133

IgG aggregates of different sizes stimulate or suppress Ig secretion by human lymphocytesin vitro

  • C. Wiesenhutter
  • D. W. Knutson
  • D. S. Musgrave
  • R. F. Ashman
Original Articles

Abstract

The regulatory effects of IgG aggregates on Ig productionin vitro by human peripheral blood lymphocytes were shown to be highly dependent on the aggregate size and the degree of mitogenic stimulation. Covalently linked oligometers of IgG were prepared with dimethylsuberimidate cross-linking and chromatographic separation; larger aggregates were prepared by heating (63°C) and preparative zonal ultracentrifugation. The storage and culture conditions used were shown to preserve the stability of aggregate sizes. Although both positive and negative regulatory effects were seen with cells isolated directly from blood, more predictable dose-related effects were seen if cells were vigorously washed, possibly due to the removal of IgG or natural immune complexes bound by the cellsin vivo. Some preparations of small IgG oligomers produced marked stimulation of Ig production, especially in cells cultured without mitogen or with suboptimal pokeweed mitogen doses. Aggregates containing six or more IgGs suppressed Ig production, especially when cells were stimulated by mitogen at optimal concentrations.

Key words

IgG aggregates regulation of Ig synthesis 

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References

  1. 1.
    Moretta L, Webb S, Grossi CE, Lydyard PW, Cooper MD: Functional analysis of two human subpopulations: Help and suppression by T cells. J Exp Med 146:184–200, 1977Google Scholar
  2. 2.
    Kaatari S, Scibienski RJ, Benjamini E: The immunoregulatory role of antigen antibody complexes. I. Assessment of B and T cell responses. Immunology 40:9–16, 1980Google Scholar
  3. 3.
    Pearlman DS: The influence of antibodies on immunologic responses. I. The effect on the response to particulate antigen in the rabbit. J Exp Med 126:127–148, 1967Google Scholar
  4. 4.
    Tite JP, Morrison CA, Taylor RB: Immunoregulatory effects of covalent antigen-antibody complexes. III. Enhancement or suppression depending on the time of administration of complex relative to a T-independent antigen. Immunology 42:355–363, 1981Google Scholar
  5. 5.
    Chan PL, Sinclair NR St C: Regulation of the immune response. V. An analysis of the function of the Fc portion of antibody in suppression of an immune response with respect to interaction with components of the lymphoid system. Immunology 21:967–981, 1971Google Scholar
  6. 6.
    Oberbarnscheidt J, Kolsch E: Direct blockade of antigen-reactive B lymphocytes by immune complexes. An “off” signal for precursors of IgM-producing cells provided by the linkage of antigen- and Fc-receptors. Immunology 35:151–157, 1978Google Scholar
  7. 7.
    Stockinger B, Lemmel E-M: Fc receptor dependency of antibody mediated feedback regulation: On the mechanism of inhibition. Cell Immunol 40:395–403, 1978Google Scholar
  8. 8.
    Nicholson JKA, McDougal JS: Aggregated IgG-induced suppression ofin vitro antibody responses: definition of the cellular target. J Immunol 126:2382–2389, 1981Google Scholar
  9. 9.
    Ryan JL, Arbett RD, Dickler HB, Henkart PA: Inhibition of lymphocyte mitogenesis by immobilized antigen-antibody complexes. J Exp Med 142:814–826, 1975Google Scholar
  10. 10.
    Setcavage TM, Kim YB: Inhibition of the immune response by Fc receptor-bound specific antibody on T lymphocytes. J Immunol 124:553–556, 1980Google Scholar
  11. 11.
    Hoffmann MK, Kappler JW: Two distinct mechanisms of immune suppression by antibody. Nature 272:64–65, 1978Google Scholar
  12. 12.
    Miyama M, Kuribayashi K, Yodoi J, Takabayashi A, Masuda T: Immunological properties of Fc receptor on lymphocytes. 1. Functional differences between Fc receptor-positive and negative lymphocytes in humoral immune responses. Cell Immunol 35:253–265, 1978Google Scholar
  13. 13.
    Yodoi J, Takabayashi A, Masuda T: Immunological properties of Fc receptor on lymphocytes. 4. Fc receptor of Con A induced suppressor and helper T cells. Cell Immunol 39:225–237, 1978Google Scholar
  14. 14.
    Fridman WH, Fradelizi D, Guimezanes A, Plater C, Leclerc JC: The role of the Fc receptor (FcR) on thymus-derived lymphocytes. II. Presence of FcR on suppressor cells and direct involvement in suppression. Eur J Immunol 8:549–554, 1977Google Scholar
  15. 15.
    Masuda T, Miyama M, Kuribayashi K, Yodoi J, Takabayashi A, Kyoizumi S: Immunological properties of Fc receptor on lymphocytes. 5. Suppressive regulation of humoral immune response by Fc receptor bearing B lymphocytes. Cell Immunol 39:238–249, 1978Google Scholar
  16. 16.
    Ptak W, Zembala M, Gershon RK: Intermediary role of macrophages in the passage of suppressor signals between T-cell subsets. J Exp Med 148:424–434, 1978Google Scholar
  17. 17.
    Taylor RB, Basten A: Suppressor cells in humoral immunity and tolerance. Br Med Bull 152–157, 1976Google Scholar
  18. 18.
    Abbas AK, Klaus GGB: Antigen-antibody complexes suppress antibody production by mouse plasmacytoma cellsin vitro. Eur J Immunol 8:217–220, 1978Google Scholar
  19. 19.
    Sinclair NR St C: Regulation of the immune response. I. Reduction in ability of specific antibody to inhibit long-lasting IgG immunological priming after removal of the Fc fragment. J Exp Med 129:1183–1201, 1969Google Scholar
  20. 20.
    LaVia MF, LaVia DS: Studies on Fc receptor function. I. IgG-mediated inhibition of B lymphocyte activation by T-independent and T-dependent antigens. Cell Immunol 39:297–306, 1978Google Scholar
  21. 21.
    Morgan EL, Thoman ML, Walker SM, Weigle WO: Regulation of the immune response. II. Characterization of the cell population(s) involved in the Fc fragment-induced adjuvant effect. J Immunol 125:1275–1279, 1980Google Scholar
  22. 22.
    Thoman ML, Weigle WO: Preliminary chemical and biologic characterization of (Fc)TRF: An Fc fragment-induced T cell-replacing factor. J Immunol 128:590–594, 1982Google Scholar
  23. 23.
    Yamasaki K, and Ziff M: Enhancement ofin vitro Ig synthesis of rheumatoid lymphocytes by aggregated human gamma globulin. Arch Rheum 20:679–684, 1977Google Scholar
  24. 24.
    Getzy DM, Clough JD, Calabrese LH, Frank SH: Regulatory effects of immune complexes onin vitro immunoglobulin synthesis. Fed Proc 40:abstr 4799, 1981Google Scholar
  25. 25.
    Segal DM, Titus JA: Subclass specificity for the binding of murine myeloma proteins to macrophage and lymphoid cell lines and to normal spleen cells. J Immunol 120:1395–1403, 1978Google Scholar
  26. 26.
    McConahey PJ, Dixon FJ: A method of trace iodination of proteins for immunologic studies. Intern Arch Allergy Appl Immunol 29:185–189, 1966Google Scholar
  27. 27.
    Knutson DW, Kijlstra A, Lentz H, vanEs LA: Isolation of stable aggregates of IgG by zonal ultracentrifugation in sucrose density gradients containing albumin. Immunol Commun 8:337–345, 1979Google Scholar
  28. 28.
    Knutson DW, Kijlstra A, vanEs LA: Association and dissociation of aggregated IgG from rat peritoneal macrophages. J Exp Med 145:1368–1381, 1977Google Scholar
  29. 29.
    Alexander EL, Titus JA, Segal DM: Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and Ficoll-Hypaque. J Immunol Meth 22:263–272, 1978Google Scholar
  30. 30.
    Kessler SW: 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 115:1617–1624, 1975Google Scholar
  31. 31.
    Saxon A, Stevens RH, Ashman RF: Regulation of immunoglobulin production in human peripheral blood lymphocytes: Cellular interactions. J Immunol 118:1782–1789, 1977Google Scholar
  32. 32.
    Sinclair NR St C: Modulation of immunity by antibody, antigen-antibody complexes and antigen. Pharmacol Ther 4:355–432, 1979Google Scholar
  33. 33.
    Mannik M, Haakenstad AO: Circulation and glomerular deposition of immune complexes. Arch Rheum 20:S148–157, 1977Google Scholar
  34. 34.
    Cochrane CG, Hawkins D: Studies on circulating immune complexes. 3. Factors governing the ability of circulating complexes to localize in blood vessels. J Exp Med 127:137–154, 1968Google Scholar
  35. 35.
    Levinsky RJ, Cameron JS, Soothill JF: Serum immune complexes and disease activity in lupus nephritis. Lancet 1:564–567, 1977Google Scholar
  36. 36.
    Halla JT, Volanakis JE, Hardin JG, Schrohenloher RE: Immune complex detection and complement activity in rheumatoid arthritis: A comparative study of a radioimmunoassay using monoclonal rheumatoid factor, gel diffusion techniques and C4 activity. Clin Exp Immunol 34:226–234, 1978Google Scholar
  37. 37.
    Chia D, Barnett EV, Yamagada J, Knutson DW, Restivo C, Furst D: Quantitation and characterization of soluble immune complexes precipitated from sera by polyethylene glycol (PEG). Clin Exp Immunol 37:399–407, 1979Google Scholar
  38. 38.
    Theofilopoulos AN, Wilson CB, Dixon FJ: The Raji cell radioimmune assay for detecting immune complexes in human sera. J Clin Invest 57:169–182, 1976Google Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • C. Wiesenhutter
    • 1
  • D. W. Knutson
    • 2
  • D. S. Musgrave
    • 3
  • R. F. Ashman
    • 3
  1. 1.Department of Microbiology/Immunology and Medicine, Center for Health SciencesUCLA School of MedicineLos Angeles
  2. 2.Division of NephrologyUniversity of Rochester School of Medicine and Dentistry, Strong Memorial HospitalRochester
  3. 3.Department of Internal Medicine, Division of RheumatologyUniversity of Iowa School of Medicine and V.A. HospitalIowa City

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