Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1983 May;71(5):1375–1382. doi: 10.1172/JCI110890

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

S Romagnani, G F Del Prete, E Maggi, G Bellesi, G Biti, P L Rossi Ferrini, M Ricci
PMCID: PMC437001  PMID: 6602150

Abstract

The immunoglobulin-synthesizing activities of peripheral blood mononuclear cells from 57 untreated patients with Hodgkin's disease and 47 normal subjects were compared. Cumulative amounts of IgM and IgG synthesized and secreted by unstimulated and pokeweed mitogen-stimulated cells over a 7-d period were determined in a solid-phase radioimmunoassay. Synthesis of IgM in unstimulated cultures and of both IgM and IgG in cultures stimulated with pokeweed mitogen was markedly reduced in patients with Hodgkin's disease, whereas the mean level of the spontaneous IgG synthesis was enhanced. The degree and frequency of in vitro abnormalities were not influenced by disease stage or histology. Depression of pokeweed mitogen-induced immunoglobulin synthesis did not correlate with excessive number of monocytes and it was unaffected by removal of phagocytic cells or addition to the cultures of monocytes from normal individuals. On the other hand, monocytes isolated from blood of patients with Hodgkin's disease were even more effective than normal monocytes in supporting pokeweed mitogen-induced immunoglobulin synthesis by normal phagocyte-depleted mononuclear cells. Synthesis of both IgM and IgG induced by pokeweed mitogen remained subnormal after addition to patient B cell cultures of autologous irradiated T cells or allogeneic normal T lymphocytes. T cells from patients with Hodgkin's disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkin's disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells to normal B cells resulted in an increase of spontaneous IgG synthesis. In patients showing depression of pokeweed mitogen-induced immunoglobulin synthesis the lymphoproliferative response and immunoglobulin synthesis stimulated by Staphylococcus aureus bacteria of the Cowan first strain, a T cell independent B cell mitogen, were also markedly reduced. These studies demonstrate impairment of immunoglobulin synthesis by cultured lymphocytes from untreated patients with Hodgkin's disease after stimulation with polyclonal B cell activators and suggest that the in vitro abnormalities may be, at least in part, the result of a preexisting in vivo activation of lymphocytes in Hodgkin's disease patients.

Full text

PDF
1375

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amlot P. L., Green L. A. Atopy and immunoglobulin E concentrations in Hodgkin's disease and other lymphomas. Br Med J. 1978 Feb 11;1(6109):327–329. doi: 10.1136/bmj.1.6109.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amlot P. L., Green L. Serum immunoglobulins G, A, M, D and E concentrations in lymphomas. Br J Cancer. 1979 Sep;40(3):371–379. doi: 10.1038/bjc.1979.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beale M. G., Nash G. S., Bertovich M. J., MacDermott R. P. Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schönlein purpura and systemic lupus erythematosus. J Immunol. 1982 Jan;128(1):486–491. [PubMed] [Google Scholar]
  4. Björkholm M., Holm G., Mellstedt H., Pettersson D. Immunological capacity of lymphocytes from untreated patients with Hodgkin's disease evaluated in mixed lymphocyte culture. Clin Exp Immunol. 1975 Dec;22(3):373–377. [PMC free article] [PubMed] [Google Scholar]
  5. Blaese R. M., Grayson J., Steinberg A. D. Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus. Am J Med. 1980 Sep;69(3):345–350. doi: 10.1016/0002-9343(80)90003-0. [DOI] [PubMed] [Google Scholar]
  6. Bobrove A. M., Miller P. Depressed in vitro B-lymphocyte differentiation in systemic lupus erythematosus. Arthritis Rheum. 1977 Sep-Oct;20(7):1326–1333. doi: 10.1002/art.1780200705. [DOI] [PubMed] [Google Scholar]
  7. Bockman R. S. Stage-dependent reduction in T colony formation in Hodgkin's disease. Coincidence with monocyte synthesis of prostaglandins. J Clin Invest. 1980 Sep;66(3):523–531. doi: 10.1172/JCI109884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
  9. Carbone P. P., Kaplan H. S., Musshoff K., Smithers D. W., Tubiana M. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res. 1971 Nov;31(11):1860–1861. [PubMed] [Google Scholar]
  10. Cohen S., Fisher B., Yoshida T., Bettigole R. E. Serum migration-inhibitory activity in patients with lymphoproliferative diseases. N Engl J Med. 1974 Apr 18;290(16):882–886. doi: 10.1056/NEJM197404182901605. [DOI] [PubMed] [Google Scholar]
  11. Corte G., Ferrarini M., Tonda P., Bargellesi A. Increased serum IgD concentrations in patients with Hodgkin's disease. Clin Exp Immunol. 1977 May;28(2):359–362. [PMC free article] [PubMed] [Google Scholar]
  12. Cowther D., Fairley G. H., Sewell R. L. Significance of the changes in the circulating lymphoid cells in Hodgkin's disease. Br Med J. 1969 May 24;2(5655):473–477. doi: 10.1136/bmj.2.5655.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Crowther D., Fairley G. H., Sewell R. L. Lymphoid cellular responses in the blood after immunization in man. J Exp Med. 1969 May 1;129(5):849–869. doi: 10.1084/jem.129.5.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DeVita V. T., Jr Lymphocyte reactivity in Hodgkin's disease: a lymphocyte civil war. N Engl J Med. 1973 Oct 11;289(15):801–802. doi: 10.1056/NEJM197310112891510. [DOI] [PubMed] [Google Scholar]
  15. Ehrnst A., Lambert B., Fagraeus A. DNA synthesis in subpopulations of blood mononuclear leucocytes in human subjects after vaccination against yellow fever. Scand J Immunol. 1978;8(4):339–346. doi: 10.1111/j.1365-3083.1978.tb00527.x. [DOI] [PubMed] [Google Scholar]
  16. Eltringham J. R., Kaplan H. S. Impaired delayed-hypersensitivity responses in 154 patients with untreated Hodgkin's disease. Natl Cancer Inst Monogr. 1973 May;36:107–115. [PubMed] [Google Scholar]
  17. Gast G. C., Halie M. R., Nieweg H. O. Immunological responsiveness against two primary antigens in untreated patients with Hodgkin's disease. Eur J Cancer. 1975 Apr;11(4):217–224. doi: 10.1016/0014-2964(75)90001-8. [DOI] [PubMed] [Google Scholar]
  18. Ginsburg W. W., Finkelman F. D., Lipsky P. E. Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus. Clin Exp Immunol. 1979 Jan;35(1):76–88. [PMC free article] [PubMed] [Google Scholar]
  19. Gmelig-Meyling F., Waldmann T. A. Human B cell activation in vitro: augmentation and suppression by monocytes of the immunoglobulin production induced by various B cell stimulants. J Immunol. 1981 Feb;126(2):529–537. [PubMed] [Google Scholar]
  20. Goodwin J. S., Messner R. P., Bankhurst A. D., Peake G. T., Saiki J. H., Williams R. C., Jr Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med. 1977 Nov 3;297(18):963–968. doi: 10.1056/NEJM197711032971802. [DOI] [PubMed] [Google Scholar]
  21. Holm G., Mellstedt H., Björkholm M., Johansson B., Killander D., Sundblad R., Söderberg G. Lymphocyte abnormalities in untreated patients with Hodgkin's disease. Cancer. 1976 Feb;37(2):751–762. doi: 10.1002/1097-0142(197602)37:2<751::aid-cncr2820370223>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  22. Huber C., Michlmayr G., Falkensamer M., Fink U., Zur Nedden G., Braunsteiner H., Huber H. Increased proliferation of T lymphocytes in the blood of patients with Hodgkin's disease. Clin Exp Immunol. 1975 Jul;21(1):47–53. [PMC free article] [PubMed] [Google Scholar]
  23. Jasin H. E., Ziff M. Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus. Arthritis Rheum. 1975 May-Jun;18(3):219–228. doi: 10.1002/art.1780180305. [DOI] [PubMed] [Google Scholar]
  24. Kurland J. I., Bockman R. Prostaglandin E production by human blood monocytes and mouse peritoneal macrophages. J Exp Med. 1978 Mar 1;147(3):952–957. doi: 10.1084/jem.147.3.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kurnick J. T., Ostberg L., Stegagno M., Kimura A. K., Orn A., Sjöberg O. A rapid method for the separation of functional lymphoid cell populations of human and animal origin on PVP-silica (Percoll) density gradients. Scand J Immunol. 1979;10(6):563–573. doi: 10.1111/j.1365-3083.1979.tb01391.x. [DOI] [PubMed] [Google Scholar]
  26. Langenhuysen M. M., Cazemier T., Houwen B., Brouwers T. M., Halie M. R., The T. H., Nieweg H. O. Antibodies to Epstein-Barr virus, cytomegalovirus, and Australia antigen in Hodgkin's disease. Cancer. 1974 Aug;34(2):262–267. doi: 10.1002/1097-0142(197408)34:2<262::aid-cncr2820340207>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  27. Levy R., Kaplan H. S. Impaired lymphocyte function in untreated Hodgkin's disease. N Engl J Med. 1974 Jan 24;290(4):181–186. doi: 10.1056/NEJM197401242900402. [DOI] [PubMed] [Google Scholar]
  28. Long J. C., Aisenberg A. C., Zamecnik M. V., Zamecnik P. C. A tumor antigen in tissue cultures derived from patients with Hodgkin's disease. Proc Natl Acad Sci U S A. 1973 May;70(5):1540–1544. doi: 10.1073/pnas.70.5.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Longmire R. L., McMillan R., Yelenosky R., Armstrong S., Lang J. E., Craddock C. G. In vitro splenic IgG synthesis in Hodgkin's disease. N Engl J Med. 1973 Oct 11;289(15):763–767. doi: 10.1056/NEJM197310112891501. [DOI] [PubMed] [Google Scholar]
  30. Matchett K. M., Huang A. T., Kremer W. B. Impaired lymphocyte transformation in Hodgkin's disease. Evidence for depletion of circulating t-lymphocytes. J Clin Invest. 1973 Aug;52(8):1908–1917. doi: 10.1172/JCI107374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mochanko K., Fejes M., Breazavscek D. M., Suarez A., Bachmann A. E. The relation between Epstein-Barr virus antibodies and clinical symptomatology and immunodeficiency in patients with Hodgkin's disease. Cancer. 1979 Dec;44(6):2065–2070. doi: 10.1002/1097-0142(197912)44:6<2065::aid-cncr2820440617>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  32. Montazeri G., Chiorazzi N., Fu S. M., Kunkel H. G. Regulatory role of circulating monocytes in the differentiative and proliferative responses of human B lymphocytes. Clin Immunol Immunopathol. 1980 May;16(1):1–10. doi: 10.1016/0090-1229(80)90160-9. [DOI] [PubMed] [Google Scholar]
  33. Nies K. M., Louie J. S. Impaired immunoglobulin synthesis by peripheral blood lymphocytes in systemic lupus erythematosus. Arthritis Rheum. 1978 Jan-Feb;21(1):51–57. doi: 10.1002/art.1780210109. [DOI] [PubMed] [Google Scholar]
  34. Okudaira K., Tanimoto K., Nakamura T., Horiuchi Y. Spontaneously enhanced in vitro immunoglobulin synthesis by B cells in systemic lupus erythematosus. Clin Immunol Immunopathol. 1980 Jul;16(3):267–278. doi: 10.1016/0090-1229(80)90132-4. [DOI] [PubMed] [Google Scholar]
  35. Order S. E., Hellman S. Pathogenesis of Hodgkin's disease. Lancet. 1972 Mar 11;1(7750):571–573. doi: 10.1016/s0140-6736(72)90360-1. [DOI] [PubMed] [Google Scholar]
  36. Romagnani S., Amadori A., Biti G., Bellesi G., Ricci M. In vitro lymphocyte response to the phytomitogens in untreated and treated patients with Hodgkin's disease. Int Arch Allergy Appl Immunol. 1976;51(3):378–389. doi: 10.1159/000231611. [DOI] [PubMed] [Google Scholar]
  37. Romagnani S., Amadori A., Giudizi M. G., Biagiotti R., Maggi E., Ricci M. Different mitogenic activity of soluble and insoluble staphylococcal protein A (SPA). Immunology. 1978 Sep;35(3):471–478. [PMC free article] [PubMed] [Google Scholar]
  38. Romagnani S., Amadori A., Maggi E., Biagiotti R., Ricci M. Study of some immunological parameters in untreated patients with Hodgkin's disease. Int Arch Allergy Appl Immunol. 1977;55(1-6):429–438. doi: 10.1159/000231954. [DOI] [PubMed] [Google Scholar]
  39. Romagnani S., Biagiotti R., Amadori A., Maggi E., Biti G., Bellesi G., Ricci M. Hyperproduction of IgE and T-cell dysfunction in Hodgkin's disease. Int Arch Allergy Appl Immunol. 1980;63(1):64–72. doi: 10.1159/000232610. [DOI] [PubMed] [Google Scholar]
  40. Romagnani S., Giudizi M. G., Biagiotti R., Almerigogna F., Maggi E., Del Prete G., Ricci M. Surface immunoglobulins are involved in the interaction of protein A with human B cells and in the triggering of B cell proliferation induced by protein A-containing Staphylococcus aureus. J Immunol. 1981 Oct;127(4):1307–1313. [PubMed] [Google Scholar]
  41. Schechter G. P., Soehnlen F. Monocyte-mediated inhibition of lymphocyte blastogenesis in Hodgkin disease. Blood. 1978 Aug;52(2):261–271. [PubMed] [Google Scholar]
  42. Siegal F. P., Siegal M. Enhancement by irradiated T cells of human plasma cell production: dissection of helper and suppressor functions in vitro. J Immunol. 1977 Feb;118(2):642–647. [PubMed] [Google Scholar]
  43. Twomey J. J., Laughter A. H., Rice L., Ford R. Spectrum of immunodeficiencies with Hodgkin's disease. J Clin Invest. 1980 Oct;66(4):629–637. doi: 10.1172/JCI109898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wagener D. J., Van Munster P. J., Haanen C. The immunoglobulins in Hodgkin's disease. Eur J Cancer. 1976 Sep;12(9):683–688. doi: 10.1016/0014-2964(76)90016-5. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES