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. 1979 Jan;35(1):76–88.

Circulating and pokeweed mitogen-induced immunoglobulin-secreting cells in systemic lupus erythematosus.

W W Ginsburg, F D Finkelman, P E Lipsky
PMCID: PMC1537595  PMID: 154983

Abstract

Peripheral blood mononuclear cells (PBM) obtained from patients with active untreated systemic lupus erythematosus (SLE) were evaluated both for the number of cells spontaneously secreting immunoglobulin (Ig) as well as for their capacity to generate immunoglobulin-secreting cells (ISC) in vitro in response to pokeweed mitogen (PWM). ISC were enumerated by a reverse haemolytic plaque assay designed to quantify the number of cells secreting IgG, IgM and IgA. PBM obtained from eight patients with active untreated SLE contained markedly increased numbers of ISC compared to age-, sex-, and race-matched normal control PBM. SLE PBM contained a mean of 13,805 +/- 3266 ISC per 10(6) cells, of which 74% secreted IgG, 10% IgM and 22% IgA, while normal PBM contained a mean of 779 +/- 143 ISC per 10(6) cells, with 57% secreting IgG, 25% IgM and 33% IgA. PBM obtained from SLE patients were also examined for their ability to generate ISC in vitro in response to PWM. SLE PBM were markedly deficient in their capacity to respond to PWM with the differentiation of ISC. This diminished responsiveness could not be ascribed to serum factors, the presence of increased numbers of cells with suppressive capacity or the absence of potentially responsive B cells. Rather, a deficiency of helper T cell activity appeared to be responsible. This was indicated by the observation that PWM responsiveness could be restored to SLE PBM by co-culturing them with purified mitomycin C-treated normal T cells.

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Selected References

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  1. Andrianakos A. A., Tsichlis P. N., Merikas E. G., Marketos S. G., Sharp J. T., Merikas G. E. Cell-mediated immunity in systemic lupus erythematosus. Clin Exp Immunol. 1977 Oct;30(1):89–96. [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Bourgois A., Kitajima K., Hunter I. R., Askonas B. A. Surface immunoglobulins of lipopolysaccharide-stimulated spleen cells. The behavior of IgM, IgD and IgG. Eur J Immunol. 1977 Mar;7(3):151–153. doi: 10.1002/eji.1830070307. [DOI] [PubMed] [Google Scholar]
  4. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  5. Cass R. M., Mongan E. S., Jacox R. F., Vaughan J. H. Immunoglobulins G, A, and M in systemic lupus erythematosus. Relationship to serum complement titer, latex titer, antinuclear antibody, and manifestations of clinical disease. Ann Intern Med. 1968 Oct;69(4):749–756. doi: 10.7326/0003-4819-69-4-749. [DOI] [PubMed] [Google Scholar]
  6. Delbarre F., Le Gô A., Kahan A. Hyperbasophilic immunoblasts in circulating blood in chronic inflammatory rheumatic and collagen diseases. Ann Rheum Dis. 1975 Oct;34(5):422–430. doi: 10.1136/ard.34.5.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fauci A. S., Pratt K. R., Whalen G. Activation of human B lymphocytes. II. Cellular interactions in the PFC response of human tonsillar and peripheral blood B lymphocytes to polyclonal activation by pokeweed mitogen. J Immunol. 1976 Dec;117(6):2100–2104. [PubMed] [Google Scholar]
  8. Finkelman F. D., Lipsky P. E. Immunoglobulin secretion by human splenic lymphocytes in vitro: the effects of antibodies to IgM and IgD. J Immunol. 1978 May;120(5):1465–1472. [PubMed] [Google Scholar]
  9. Ginsburg W. W., Finkelman F. D., Lipsky P. E. Circulating and mitogen-induced immunoglobulin-secreting cells in human peripheral blood: evaluation by a modified reverse hemolytic plaque assay. J Immunol. 1978 Jan;120(1):33–39. [PubMed] [Google Scholar]
  10. HARVEY A. M., SHULMAN L. E., TUMULTY P. A., CONLEY C. L., SCHOENRICH E. H. Systemic lupus erythematosus: review of the literature and clinical analysis of 138 cases. Medicine (Baltimore) 1954 Dec;33(4):291–437. [PubMed] [Google Scholar]
  11. Herman J. H., Bradley J., Ziff M., Smiley J. D. Response of the rheumatoid synovial membrane to exogenous immunization. J Clin Invest. 1971 Feb;50(2):266–273. doi: 10.1172/JCI106491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horwitz D. A., Cousar J. B. A relationship between impaired cellular immunity humoral suppression of lymphocyte function and severity of systemic lupus erythematosus. Am J Med. 1975 Jun;58(6):829–835. doi: 10.1016/0002-9343(75)90639-7. [DOI] [PubMed] [Google Scholar]
  13. Hulliger L., Sorkin E. Formation of specific antibody by circulating cells. Immunology. 1965 Oct;9(4):391–401. [PMC free article] [PubMed] [Google Scholar]
  14. Hurd E. R., Dowdle W., Casey H., Ziff M. Virus antibody levels in systemic lupus erythematosus. Arthritis Rheum. 1972 May-Jun;15(3):267–274. doi: 10.1002/art.1780150308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Janossy G., Greaves M. Functional analysis of murine and human B lymphocyte subsets. Transplant Rev. 1975;24:177–236. doi: 10.1111/j.1600-065x.1975.tb00169.x. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Kay J. E., Korner A. Effect of cycloheximide on protein and ribonucleic acid synthesis in cultured human lymphocytes. Biochem J. 1966 Sep;100(3):815–822. doi: 10.1042/bj1000815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Keightley R. G., Cooper M. D., Lawton A. R. The T cell dependence of B cell differentiation induced by pokeweed mitogen. J Immunol. 1976 Nov;117(5 Pt 1):1538–1544. [PubMed] [Google Scholar]
  19. LANDY M., SANDERSON R. P., BERNSTEIN M. T., JACKSON A. L. ANTIBODY PRODUCTION BY LEUCOCYTES IN PERIPHERAL BLOOD. Nature. 1964 Dec 26;204:1320–1321. doi: 10.1038/2041320a0. [DOI] [PubMed] [Google Scholar]
  20. Lies R. B., Messner R. P., Williams R. C., Jr Relative T-cell specificity of lymphocytotoxins from patients with systemic lupus erythematosus. Arthritis Rheum. 1973 May-Jun;16(3):369–375. doi: 10.1002/art.1780160312. [DOI] [PubMed] [Google Scholar]
  21. Lipsky P. E., Ginsburg W. W., Finkelman F. D., Ziff M. Control of human B lymphocyte responsiveness: enhanced suppressor T cell activity after in vitro incubation. J Immunol. 1978 Mar;120(3):902–910. [PubMed] [Google Scholar]
  22. Lipsky P. E., Ziff M. Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds. J Clin Invest. 1977 Mar;59(3):455–466. doi: 10.1172/JCI108660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lockshin M. D., Eisenhauer A. C., Kohn R., Weksler M., Block S., Mushlin S. B. Cell-mediated immunity in rheumatic diseases. II. Mitogen responses in RA, SLE, and other illnesses: correlation with T- and B-lymphocyte populations. Arthritis Rheum. 1975 May-Jun;18(3):245–250. doi: 10.1002/art.1780180308. [DOI] [PubMed] [Google Scholar]
  24. MICHAEL S. R., VURAL I. L., BASSEN F. A., SCHAEFER L. The hematologic aspects of disseminated (systemic) lupus erythematosus. Blood. 1951 Nov;6(11):1059–1072. [PubMed] [Google Scholar]
  25. Messner R. P., Lindström F. D., Williams R. C., Jr Peripheral blood lymphocyte cell surface markers during the course of systemic lupus erythematosus. J Clin Invest. 1973 Dec;52(12):3046–3056. doi: 10.1172/JCI107503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Phillips P. E., Christian C. L. Virus antibodies in systemic lupus erythematosus and other connective tissue diseases. Ann Rheum Dis. 1973 Sep;32(5):450–456. doi: 10.1136/ard.32.5.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rosenthal C. J., Franklin E. C. Depression of cellular-mediated immunity in systemic lupus erythematosus. relation to disease activity. Arthritis Rheum. 1975 May-Jun;18(3):207–217. doi: 10.1002/art.1780180303. [DOI] [PubMed] [Google Scholar]
  28. Rothfield N. F., Evans A. S., Niederman J. C. Clinical and laboratory aspects of raised virus antibody titres in systemic lupus erythematosus. Ann Rheum Dis. 1973 May;32(3):238–246. doi: 10.1136/ard.32.3.238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scheinberg M. A., Cathcart E. S. B cell and T cell lymphopenia in systemic lupus erythematosus. Cell Immunol. 1974 May;12(2):309–314. doi: 10.1016/0008-8749(74)90083-5. [DOI] [PubMed] [Google Scholar]
  30. Stastny P., Ziff M. Antibodies against cell membrane constituents in systemic lupus erythematosus and related diseases. I. Cytotoxic effect of serum from patients with systemic lupus erythematosus (SLE) for allogeneic and for autologous lymphocytes. Clin Exp Immunol. 1971 Apr;8(4):543–550. [PMC free article] [PubMed] [Google Scholar]
  31. Terasaki P. I., Mottironi V. D., Barnett E. V. Cytotoxins in disease. Autocytotoxins in lupus. N Engl J Med. 1970 Oct 1;283(14):724–728. doi: 10.1056/NEJM197010012831403. [DOI] [PubMed] [Google Scholar]
  32. Thomson P. D., Harris N. S. Detection of plaque-forming cells in the peripheral blood of actively immunized humans. J Immunol. 1977 Apr;118(4):1480–1482. [PubMed] [Google Scholar]
  33. Utsinger P. D., Yount W. J. Phytohemagglutinin response in systemic lupus erythematosus. Reconstitution experiments using highly purified lymphocyte subpopulations and monocytes. J Clin Invest. 1977 Sep;60(3):626–638. doi: 10.1172/JCI108814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wernet P., Kunkel H. G. Antibodies to a specific surface antigen of T cells in human sera inhibiting mixed leukocyte culture reactions. J Exp Med. 1973 Oct 1;138(4):1021–1026. doi: 10.1084/jem.138.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Williams R. C., Jr, Lies R. B., Messner R. P. Inhibition of mixed leukocyte culture responses by serum and gamma-globulin fractions from certain patients with connective tissue disorders. Arthritis Rheum. 1973 Sep-Oct;16(5):597–605. doi: 10.1002/art.1780160504. [DOI] [PubMed] [Google Scholar]
  36. Winchester R. J., Winfield J. B., Siegal F., Wernet P., Bentwich Z., Kunkel H. G. Analyses of lymphocytes from patients with rheumatoid arthritis and systemic lupus erythematosus. Occurrence of interfering cold-reactive antilymphocyte antibodies. J Clin Invest. 1974 Nov;54(5):1082–1092. doi: 10.1172/JCI107852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Winfield J. B., Winchester R. J., Wernet P., Fu S. M., Kunkel H. G. Nature of cold-reactive antibodies to lymphocyte surface determinants in systemic lupus erythematosus. Arthritis Rheum. 1975 Jan-Feb;18(1):1–8. doi: 10.1002/art.1780180101. [DOI] [PubMed] [Google Scholar]
  38. van Furth R., Schuit H. R., Hijmans W. The formation of immunoglobulins by human tissues in vitro. IV. Circulating lymphocytes in normal and pathological conditions. Immunology. 1966 Jul;11(1):29–40. [PMC free article] [PubMed] [Google Scholar]

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