Skip to main content
SpringerLink
Log in

The defect in peripheral blood B-cell activation in patients with multiple myeloma is not due to a deficiency in the production of B-cell growth and differentiation factors

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

The suppression of B lymphopoiesis is a major feature of multiple myeloma (MM). In this disease, there is a striking defect in the response of peripheral blood B cells to pokeweed mitogen (PWM). Normally, B-cell activation depends on B-cell growth factors (BCGFs) and B-cell differentiation factors (BCDFs), produced by peripheral blood mononuclear cells. We therefore evaluated whether the production of these cytokines was defective in patients with MM. We have studied the production of BCGFs (using the anti-μ assay) and, particularly, interleukin-2 and interferon-γ, two well-documented BCGFs. No defect in the production of BCGFs, interleukin-2, and interferon-γ was found in patients with active (N=14) or stable (N=10) MM, compared with healthy donors (N=13). The production of BCDFs (i.e., overall activity) was also evaluated and, more particularly, that of interleukin-6 (IL-6). This cytokine is a potent BCDF which is essential in the PWM-induced activation of B cells, acting at the terminal stages of B-cell differentiation. Again, no defect in the production of BCDFs and IL-6 was found in patients with MM. Therefore, the ability to secrete cytokines controlling the process of B-cell activation is not affected in such patients. This indicates that the profound failure of humoral immune response is not due to deficiency of peripheral blood mononuclear cells producing these factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Google Scholar 

  2. Knapp W, Baumgartner G: Monocyte mediated suppression of human B lymphocyte differentiation in vitro. J Immunol 121:1177–1182, 1978

    Google Scholar 

  3. Twomey JJ, Laughter AH, Rice L, Ford RJ: Suppression of lymphocyte responses by monocytes with untreated and treated Multiple myeloma. Blood 60:316–322, 1982

    Google Scholar 

  4. Takeshita A: Regulation of immunoglobulin synthesis by monocytes in multiple myeloma and benign monoclonal gammapathy Clin Exp Immunol 67:625–632, 1986

    Google Scholar 

  5. Kishimoto T: B-cell stimulatory factors (BSFs): Molecular structure, biological function, and regulation of expression. J Clin Immunol 7:343–355, 1987

    Google Scholar 

  6. Kishimoto T, Yoshizaki K, Okada M, Kuritani T, Kikutani H, Sakaguchi N, Miki Y, Nakagawa T, Shimizu K, Fukanaga K, Taga T: Growth and differentiation factors and activation of human B-cells. Lymphokines 10:15–24, 1985

    Google Scholar 

  7. Gordon J, Guy GR: The molecules controlling B lymphocytes. Immunol Today 8:339–344, 1987

    Google Scholar 

  8. Romagnani S, Giudizi GM, Maggi E, Almerigogna F, Biagotti R, Del Prete G, Mazetti M, Alessi A, Vercelli D, Ricci M: Synergy of B cell growth and interleukin 2 in the proliferation of activated human B cells. Eur J Immunol 15:1158–1164, 1985

    Google Scholar 

  9. Romagnani S, Grazia Guidizi M, Almerigogna F, Biagotti R, Alessi A, Mingari C, Liang C, Moretta L, Ricci M: Analysis of the role of interferon-gamma, interleukin 2 and a third factor distinct from interferon-gamma and interleukin 2 on human B cell proliferation. Evidence that they act at different times after B cell activation. Eur J Immunol 16:623–629, 1986

    Google Scholar 

  10. Romagnani S, Del Prete G, Giudizi MG, Biagotti R, Almerigogna F, Tiri A, Mazetti M, Ricci M: Direct induction of human B-cell differentiation by recombinant interleukin-2. Immunology 58:31–35, 1986

    Google Scholar 

  11. Lê Thi Bich Thuy Queen C, Fauci AS: Interferon-γ induces light chain synthesis in interleukin 2 stimulated human B cells. Eur J Immunol 16:547–550, 1986

    Google Scholar 

  12. Aarden LA, De Groot ER, Schaap OL, Lansdorp PM: Production of hybridoma growth factor by human monocytes. Eur J Immunol 17:1411–1416, 1987

    Google Scholar 

  13. Content J, Dewit L, Pierard D, Derynck R, Declerq E, Fiers W: Secretory proteins induced in human fibroblasts under conditions used for the production of interferon-β. Proc Natl Acad Sci 79:2768–2772, 1982

    Google Scholar 

  14. Billiau A: BSF-2 is not just a differentiation factor. Nature 324:415–415, 1986

    Google Scholar 

  15. Gauldie J, Richards C, Harnish D, Landsdorp P, Baumann H: Interferon-β2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci 84:7251–7255, 1987

    Google Scholar 

  16. Garman RD, Jacobs KA, Clark SC, Raulet DH: B-cell-stimulating factor 2 (β2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci 84:7629–7633, 1987

    Google Scholar 

  17. Hirano T, Kuritani T, Kishimoto T, Yamamura Y: In vitro immune response of human peripheral lymphocytes. I. The mechanism(s) involved in T cell helper functions in the pokeweed mitogen-induced differentiation and proliferation of B cells. J Immunol 119:1235–1241, 1977

    Google Scholar 

  18. Hirano T, Teranishi T, Toba H, Sakagushi N, Fukukawa T, Tsuyuguchi I: Human helper T cell factor(s) (THF). I. Partial purification and characterisation. J Immunol 126:517–522, 1981

    Google Scholar 

  19. Durie BGM, Salmon SE: Multiple myeloma, macroglobulinemia and monoclonal gammapathies.In Recent Advances in Haematology, AV Hoffbrand, MC Brain, J Hirsh (eds). New York, Churchill Livingstone, 1977, pp 243–261

    Google Scholar 

  20. Bataille R, Dessauw P, Sany J: Polyclonal immunoglobulins in malignant plasma cell dyscrasias. Oncology 41:314–317, 1984

    Google Scholar 

  21. Bataille R, Souteyrand P, Sany J: Clinical evaluation of response or escape to chemotherapy and survival of patients with multiple myeloma. A prospective study of 202 patients. Anticancer Res 4:339–346, 1984

    Google Scholar 

  22. Böyum A: Separation of lymphocytes from blood and bone marrow. Scand J Clin Lab Invest 21:77–80, 1968

    Google Scholar 

  23. Preud'homme JL, Flandrin G: Identification by peroxydase staining of monocytes in surface immunofluorescence tests. J Immunol 113:1650–1655, 1971

    Google Scholar 

  24. Caraux J, Thierry C, Serrou B: Quantitative comparison of K cell potential in human T and null cells. Eur J Immunol 8:806–812, 1978

    Google Scholar 

  25. Klein B, Rey A, Jourdan M: The role of interleukin 1 and interleukin 2 in T-human colony formation. Cell Immunol 77:348–356, 1983

    Google Scholar 

  26. Vandamme JV, Cayphas S, Opdenakker G, Billiau A, Van snick J: Interleukin 1 and poly(rI)·poly(rC) induce production of a hybridoma growth factor by human fibroblasts. Eur J Immunol 17:1–7, 1987

    Google Scholar 

  27. Bonnard GD, Yasaka K, Maca RD: Continued growth of functional T lymphocytes: Production of human T-cell growth factor. Cell Immunol 51:390–401, 1980

    Google Scholar 

  28. Rossi JF, Klein B, Commes T, Jourdan M: Interleukin 2 production in B cell chronic lymphocytic leukemia. Blood 66:840–846, 1985

    Google Scholar 

  29. Insel RA, Merler E: The necessity for T cell help for human tonsil B cell responses to pokeweed mitogen: Induction of DNA synthesis, immunoglobulin, and specific antibody production with a T cell helper factor produced with pokeweed mitogen. J Immunol 118:2009–2014, 1977

    Google Scholar 

  30. Chouaib S, Fradelizi D: The mechanism of inhibition of IL2 production. J Immunol 129:2463–2468, 1982

    Google Scholar 

  31. Kehrl JH, Wakefield LM, Roberts AB, Jakowlew S, Alvarez-mon M, Derynck R, Sporn MB, Fauci AS: Production of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med 163:1037–1050, 1986

    Google Scholar 

  32. Kerhl HJ, Roberts AB, Wakefields LM, Jakowlew S, Sporn MB, Fauci AS: Transforming growth factor β is an important immunomodulatory protein for human B lymphocytes. J Immunol 137:3855–3860, 1986

    Google Scholar 

  33. Blomhoff HK, Smeland E, Mustafa AS, Godal T, Ohlsson R: Epstein-Barr virus mediates a switch in responsiveness to transforming growth factor, type beta, in cells of the B cell lineage. Eur J Immunol 17:299–301, 1987

    Google Scholar 

  34. Seligmann M, Preud'homme JL, Brouet JC: B and T cell markers in human proliferative blood diseases and primary immunodeficiencies with special reference to membrane bound immunoglobulins. Transplant Rev 16:85–113, 1973

    Google Scholar 

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

    Google Scholar 

  36. Pilarsky LM, Mant MJ, Ruether BA, Belch A: Severe deficiency of B lymphocytes in peripheral blood for multiple myeloma patients. J Clin Invest 74:1301–1306, 1984

    Google Scholar 

  37. Zhang XG, Klein B, Brochier J, Duperray C, Bataille R: Delay and not deficiency in cap formation of peripheral blood B-cells in patients with multiple myeloma. J Clin Immunol 8:244–249, 1988

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INSERM U291. Immunopathologie des maladies tumorales et autoimmunes, ZOLAD, 99 rue Puech Villa, 34100, Montpellier Cedex, France

    Thérèse Commes, Bernard Klein, Michel Jourdan, Gisèle Clofent & Régis Bataille

  2. Ludwig Institute for Cancer Research, 74 Avenue Hippocrate, UCL 74-59, B-1200, Brussels, Belgium

    Frédéric Houssiau

  3. Laboratoire de Radioimmunologie, Centre régional de lutte contre le cancer, 34033, Montpellier Cedex, France

    Jean Grenier

  4. Consultation d'Immunorhumatologie, Centre Gui-de-Chauliac, Hopital Saint-Eloi, 34059, Montpellier Cedex, France

    Régis Bataille

Authors
  1. Thérèse Commes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernard Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michel Jourdan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gisèle Clofent
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Frédéric Houssiau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jean Grenier
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Régis Bataille
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Commes, T., Klein, B., Jourdan, M. et al. The defect in peripheral blood B-cell activation in patients with multiple myeloma is not due to a deficiency in the production of B-cell growth and differentiation factors. J Clin Immunol 9, 65–73 (1989). https://doi.org/10.1007/BF00917129

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00917129

Key words

Search

Navigation