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PWM-induced generation of immunoglobulin-secreting cells in patients with multiple myeloma

PWM-induzierte Aktivierung von Immunoglobulin-sezernierenden Zellen bei Patienten mit Multiplem Myelom

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Summary

The pokeweed-mitogen-induced transformation of B-lymphocytes into immunoglobulin-secreting cells was studied in vitro in 25 patients with multiple myeloma using a reverse hemolytic plaque assay. Fifteen patients showed a good response in generating immunoglobulin-secreting cells, whereas 10 patients showed a decreased B cell reactivity which was not due to intermittent melphalan/steroid therapy administered to 15 patients. Experiments with lymphocyte subpopulations demonstrated that the inability of some multiple-myeloma patients to generate immunoglobulin-secreting cells was always based on a defect in the B-cell subset. Co-culture experiments with lymphocytes from normal individuals and patients revealed a cell-mediated suppression in one case, whereas humoral suppressive factors in the patients' serum could not be observed using the reverse hemolytic plaque assay. Patients were classified into three groups: (a) patients with a normal B-cell function, (b) patients with a reversible, tumor-dependent suppression of B-cell reactivity and (c) patients in whom the normal B-cell population was replaced by non-reactive cells.

Zusammenfassung

Die durch Pokeweed Mitogen induzierte Transformation von B Lymphozyten in Immunglobulin-sezernierende Zellen wurde bei 25 Patienten mit multiplem Myelom in einem indirekten Plaque Assay untersucht. Fünfzehn Patienten zeigten ein normales Verhalten bezüglich der Zahl der Immunglobulin-sezernierenden Zellen, während 10 Patienten eine erniedrigte B Zell Reaktivität aufwiesen, die nicht auf eine bei 15 Patienten angewandte Melphalan/Steroid Therapie bezogen werden konnte. Experimente mit Lymphozyten-Subpopulationen zeigten, daß die bei einigen Patienten fehlende Transformationsfähigkeit immer allein auf einem Defekt der B Zell-Population beruhte. In Ko-Kulturexperimenten mit Lymphozyten von Normalpersonen und von Patienten mit multiplem Myelom konnte in einem Fall eine zellvermittelte Suppression festgestellt werden, während humorale supprimierende Faktoren im Serum von Patienten mit der angewandten Technik des indirekten Plaque Assays nicht nachgewiesen werden konnten. Die Patienten ließen sich in 3 Gruppen einteilen: (a) Patienten mit einer normalen B Zellfunktion, (b) Patienten mit einer reversiblen, tumorabhängigen Suppression der B Zellreaktivität und (c) Patienten, bei denen die normale B Zellpopulation durch nicht reaktive Zellen ersetzt war.

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Abbreviations

Ig:

Immunoglobulin(s)

RHPA:

Reverse hemolytic plaque assay

ISC:

Immunoglobulin-secreting cells

PWM:

Pokeweed mitogen

FCS:

Fetal calf serum

MM:

Multiple Myeloma

References

  1. Adler WH, Takiguchi T, Smith RT (1971) Phytohemagglutinin unresponsiveness in mouse spleens induced by methylcholanthrene sarcomas. Cancer Res 31:864–867

    Google Scholar 

  2. Alexanian R, Migliore PJ (1970) Normal immunoglobulins in multiple myeloma: effect of melphalan chemotherapy. J Lab Clin Med 75:225–233

    Google Scholar 

  3. Alper CA, Freeman T, Waldenström J (1963) The metabolism of gamma globulins in multiple myeloma and allied conditions. J Clin Invest 42:1858–1868

    Google Scholar 

  4. Barth WF, Wochner RD, Waldmann TA, Fahey JL (1964) Metabolism of human gamma macroglobulins. J Clin Invest 43:1036–1048

    Google Scholar 

  5. Bhoopalam N, Yakulis V, Costea N, Heller P (1972) Surface immunoglobulins of circulating lymphocytes in mouse plasmacytoma. II. The influence of plasmacytoma RNA on surface immunoglobulins of lymphocytes. Blood 39:465–471

    Google Scholar 

  6. Broder S, Humphrey R, Durm M, Blackman M, Meade B, Goldman C, Strober W, Waldmann T (1975) Impaired synthesis of polyclonal (non-paraprotein) immunoglobulins by circulating lymphocytes from patients with multiple myeloma. N Engl J Med 293:887–892

    Google Scholar 

  7. Brooks WH, Netsky MG, Normansell DE, Horwitz DA (1972) Depressed cell-mediated immunity in patients with primary intracranial tumors. Characterization of a humoral immunosuppressive factor. J Exp Med 136:1631–1647

    Google Scholar 

  8. Caggiano V, Cuttner J, Solomon A (1967) Myeloma proteins, Bence Jones proteins and normal immunoglobulins in multiple myeloma. Blood 30:265–287

    Google Scholar 

  9. Chen Y, Bhoopalam N, Yakulis V, Heller P (1975) Changes in lymphocyte surface immunoglobulins in myeloma and the effect of an RNA-containing plasma factor. Ann Int Med 83:625–631

    Google Scholar 

  10. Cone L, Uhr JW (1964) Immunological deficiency disorders associated with chronic lymphocytic leukemia and multiple myeloma. J Clin Invest 43:2241–2248

    Google Scholar 

  11. Cwynarski MT, Cohen S (1971) Polyclonal immunoglobulin deficiency in myelomatosis and macroglobulinaemia. Clin Exp Immunol 8:237–248

    Google Scholar 

  12. Douglas SD, Kamin RM, Fudenberg HH (1969) Human lymphocyte response to phytomitogens in vitro: normal, agammaglobulinemic and paraproteinemic individuals. J Immunol 103:1185–1195

    Google Scholar 

  13. Fahey JL, Humphrey JH (1962) Effect of transplantable plasma-cell tumors on antibody response in mice. Immunology 5:110–115

    Google Scholar 

  14. Fahey JL, Scoggins R, Utz JF, Szwed F (1963) Infection, antibody response and γ-globulin components in multiple myeloma and macroglobulinaemia. Am J Med 35:698–707

    Google Scholar 

  15. Fanger MW, Pelley RP, Reese AL (1972) In vitro demonstration of two antigenically-distinct rabbit lymphocyte populations. J Immunol 109:294–303

    Google Scholar 

  16. Friedman H, Ceglowski WS (1968) Cellular basis for the immunosuppressive properties of a leukaemogenic virus. Nature (Lond) 218:1232–1234

    Google Scholar 

  17. Furth R van, Schuit HRE, Hijmans W (1966) The formation in vitro of paraproteins in multiple myeloma and Waldenström's macroglobulinaemia. Br J Haematol 12:202–211

    Google Scholar 

  18. Gatti RA, Garrioch DB, Good RA (1970) Depressed PHA responses in patients with non-lymphoid malignancies. In: Harris JE (ed) Proceedings fifth leukocyte culture conference. Academic Press, New York, pp 339–358

    Google Scholar 

  19. Giacomoni D, Yakulis V, Wang SR, Cooke A, Dray S, Heller P (1974) In vitro conversion of normal mouse lymphocytes by plasmacytoma RNA to express idiotypic specificities on their surface characteristic of the plasmacytoma immunoglobulin. Cell Immunol 11:389–400

    Google Scholar 

  20. Good RA, Kelly WD, Rotstein J, Vargo RL (1962) Immunological deficiency diseases. Agammaglobulinemia, hypogammaglobulinemia, Hodgkin's disease and sarcoidosis. Progr Allergy 6:187–319

    Google Scholar 

  21. Gronowicz E, Coutinho A, Melchers F (1976) A plaque assay for all cells secreting Ig of a given type of class. Eur J Immunol 6:588–590

    Google Scholar 

  22. Hobbs JR (1969) Immunochemical classes of myelomatosis. Br J Haematol 16:599–606

    Google Scholar 

  23. Janossy G, Greaves MF (1971) Lymphocyte activation. I. Response of T and B lymphocytes to phytomitogens. Clin Exp Immunol 9:483–498

    Google Scholar 

  24. Kennard J, Zolla-Pazner S (1980) Origin and function of suppressor macrophages in myeloma. J Immunol 124:268–273

    Google Scholar 

  25. Kirchner H, Heberman RB, Glaser M, Larvin DH (1974) Suppression of in vitro lymphocyte stimulation in mice bearing primary Molonea sarcoma-induced tumors. Cell Immunol 13:32–40

    Google Scholar 

  26. Mabry RJ, Shelburne J, Cohen HJ (1977) In vitro kinetics of immunoglobulin synthesis by nonsecretory human myeloma cells. Blood 50:1031–1038

    Google Scholar 

  27. MacKenzie MR, Paglieroni T (1976) Studies on the pathogenesis of the immune defect in multiple myeloma. Clin Res 24:148A

    Google Scholar 

  28. MacKenzie MR, Paglieroni T (1977) Multiple myeloma: An immunologic profile. I. Peripheral blood studies. J Immunol 118:1864–1871

    Google Scholar 

  29. McKelvey EM, Fahey JL (1965) Immunoglobulin changes in disease: Quantitation on the basis of heavy polypeptide chains, IgG (G), IgA (A), and IgM (M), and of light polypeptide chains, Type K (I) and Type L (II). J Clin Invest 44:1778–1787

    Google Scholar 

  30. Mellstedt H, Hammarström E, Holm G (1974) Monoclonal lymphocyte population in human plasma cell myeloma. Clin Exp Immunol 17:371–384

    Google Scholar 

  31. Ossermann EF (1978) Multiple myeloma and related plasma cell dyscrasias. In: Samter M (ed) Immunological diseases. Little, Brown & Co, Boston, pp 499–529

    Google Scholar 

  32. Miller DG, Karnofsky DA (1961) Immunologic factors and resistance to infection in chronic lymphatic leukemia. Am J Med 31:748–757

    Google Scholar 

  33. Munoz J, Pryjma J, Fudenberg HH, Virella G (1980) Immunoglobulin quantitation and enumeration of immunoglobulin-producing cells: Comparison of two indexes of B-cell activation. Scand J Immunol 12:345–353

    Google Scholar 

  34. Preud'Homme JL, Hurez D, Danon F, Brouet JC, Seligmann M (1976) Intracytoplasmic and surface bound immunoglobulins in ‘nonsecretory’ and Bence-Jones myeloma. Clin Exp Immunol 25:428–436

    Google Scholar 

  35. Rühl H, Enders B, Bur M, Sieber G (1981) Impaired B-lymphocyte reactivity in patients with Hodgkin's disease and non-Hodgkin-lymphomas. Blut 42:271–281

    Google Scholar 

  36. Rühl H, Kirchner H (1978) Monocyte-dependent stimulation of human T cells by zinc. Clin Exp Immunol 32:484–488

    Google Scholar 

  37. Rühl H, Rühl U, Sieber G (1980) Immune alterations in patients with Hodgkin's disease. Cell Mol Biol 25:409–414

    Google Scholar 

  38. Rühl H, Scholle H, Bochert G, Vogt W (1978) Activation of lymphocyte subpopulations in patients with chronic lymphocytic leukemia. Zeitschr Immunol Forsch 154:75–87

    Google Scholar 

  39. Salmon SE (1973) Immunoglobulin synthesis and tumor kinetics of multiple myeloma. Seminars Hematol 10:135–147

    Google Scholar 

  40. Scharff MD, Uhr JW (1965) Immunologic deficiency disorders associated with lymphoproliferative diseases. Seminars Hematol 2:47–67

    Google Scholar 

  41. Sieber G, Bochert G, Enders B, Rühl H (1980) Characteristics of immunoglobulin secretion in man evaluated by a reverse hemolytic plaque assay. Blut 41:81–92

    Google Scholar 

  42. Siegel BV, Morton JI (1966) Depressed antibody response in the mouse infected with Rauscher leukaemia virus. Immunology 10:559–562

    Google Scholar 

  43. Smith E, Carlson PJ, Koenig S (1969) Plaque-forming spleen cells following irradiation of X5563 tumor. Proc Soc Exp Biol Med 130:530–534

    Google Scholar 

  44. Smith F, Grenan MM, Owens J (1960) Effect of a transplanted plasma-cell tumor on antibody formation. J Natl Cancer Inst 25:803–812

    Google Scholar 

  45. Solomon A, Waldmann TA, Fahey JL (1963) Clinical and experimental metabolism of normal 6.6S γ-globulin in normal subjects and in patients with macroglobulinemia and multiple myeloma. J Lab Clin Med 62:1–17

    Google Scholar 

  46. Solowey AC, Rapaport FT (1965) Immunologic responses in cancer patients. Surg Gynecol Obstet 121:756–760

    Google Scholar 

  47. Tanapatchaiyapong P, Zolla S (1974) Humoral immunosuppressive substance in mice bearing plasmacytoma. Science 186:748–750

    Google Scholar 

  48. Waldmann TA, Strober W (1969) Metabolism of immunoglobulins. Progr Allergy 13:1–110

    Google Scholar 

  49. Yakulis V, Bhoopalam N, Schade S, Heller P (1972) Surface immunoglobulins of circulating lymphocytes in mouse plasmacytoma. I. Characteristics of lymphocyte surface immunoglobulins. Blood 39:453–464

    Google Scholar 

  50. Zolla S (1972) The effect of plasmacytomas on the immune response of mice. J Immunol 108:1039–1048

    Google Scholar 

  51. Zolla-Pazner S, Sullivan B, Richardson D (1976) Cellular specificity of plasmacytoma-induced immunosuppression. J Immunol 117:563–568

    Google Scholar 

  52. Zolla S, Naor D, Tanapatchaiyapong P (1974) Cellular basis of immunodepression in mice with plasmacytomas. J Immunol 112:2068–2076

    Google Scholar 

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Supported by the Deutsche Forschungsgeminschaft (Ru 21 5/2)

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Sieber, G., Enders, B. & Rühl, H. PWM-induced generation of immunoglobulin-secreting cells in patients with multiple myeloma. Klin Wochenschr 59, 1101–1108 (1981). https://doi.org/10.1007/BF01746197

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  • DOI: https://doi.org/10.1007/BF01746197

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