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. 1985 Nov;76(5):1865–1870. doi: 10.1172/JCI112180

Spontaneous immunoglobulin A secretion and lack of mitogen-responsive B cells in systemic lupus erythematosus.

O Saiki, Y Saeki, S Kishimoto
PMCID: PMC424227  PMID: 3932473

Abstract

In an analysis of lymphocyte functions of systemic lupus erythematosus (SLE) patients, B cell abnormalities such as a lack of mitogen-responsive B cells and a predominance of spontaneous IgA-secreting cells (SC) were found. Lymphocyte functions of 20 SLE patients were studied. Impaired proliferative response to B cell mitogen, Staphylococcus aureus strain Cowan I (Cowan I), was observed, whereas the response to T cell mitogen phytohemagglutinin was normal. High levels of spontaneous IgA-SC were observed in SLE patients (greater than 10(2) cells/10(4) peripheral blood mononuclear cells [PBMC]), whereas spontaneous IgM-, IgG-, or IgE-SC were not proportionately increased. The number of spontaneous IgA-SC decreased with time in culture and became undetectable by day 5 of culture. In contrast, spontaneous immunoglobulin- (IgM, IgG, and IgA) SC were not observed in healthy volunteers (less than 10 cells/10(4) PBMC). Moreover, in SLE patients failure of induction of immunoglobulin-secreting cells (ISC) was observed when B cells were stimulated by Cowan I and B cell differentiation factor at any day tested, whereas ISC were induced in healthy volunteers on day 6 of culture. Depletion of T cells or macrophages did not affect the results obtained. These results suggest that the abnormalities observed in SLE B cells are not due to the in vitro direct effects of suppressor macrophages or suppressor T cells, and that the condition of the predominance of spontaneous IgA-SC and the unresponsiveness to exogenous stimulation may be emblematic of hyperactive B cells in SLE.

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Selected References

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  1. 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]
  2. Bresnihan B., Jasin H. E. Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest. 1977 Jan;59(1):106–116. doi: 10.1172/JCI108607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Budman D. R., Merchant E. B., Steinberg A. D., Doft B., Gershwin M. E., Lizzio E., Reeves J. P. Increased spontaneous activity of antibody-forming cells in the peripheral blood of patients with active SLE. Arthritis Rheum. 1977 Apr;20(3):829–833. doi: 10.1002/art.1780200312. [DOI] [PubMed] [Google Scholar]
  4. Burns G. F., Librach C. L., Frazer I. H., Kronborg I. J., Mackay I. R. Spontaneous reverse hemolytic plaque formation. III. Monocyte-mediated suppression of elevated plaque formation in autoimmune disease. Clin Immunol Immunopathol. 1982 Sep;24(3):386–395. doi: 10.1016/0090-1229(82)90009-5. [DOI] [PubMed] [Google Scholar]
  5. Decker J. L., Steinberg A. D., Reinertsen J. L., Plotz P. H., Balow J. E., Klippel J. H. NIH conference. Systemic lupus erythematosus: evolving concepts. Ann Intern Med. 1979 Oct;91(4):587–604. doi: 10.7326/0003-4819-91-4-587. [DOI] [PubMed] [Google Scholar]
  6. Deguchi H., Suemura M., Ishizaka A., Ozaki Y., Kishimoto S., Yamamura Y., Kishimoto T. IgE class-specific suppressor T cells and factors in humans. J Immunol. 1983 Dec;131(6):2751–2756. [PubMed] [Google Scholar]
  7. Delfraissy J. F., Segond P., Galanaud P., Wallon C., Massias P., Dormont J. Depressed primary in vitro antibody response in untreated systemic lupus erythematosus. T helper cell defect and lack of defective suppressor cell function. J Clin Invest. 1980 Jul;66(1):141–148. doi: 10.1172/JCI109827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Elson C. O., Heck J. A., Strober W. T-cell regulation of murine IgA synthesis. J Exp Med. 1979 Mar 1;149(3):632–643. doi: 10.1084/jem.149.3.632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Estes D., Christian C. L. The natural history of systemic lupus erythematosus by prospective analysis. Medicine (Baltimore) 1971 Mar;50(2):85–95. doi: 10.1097/00005792-197103000-00001. [DOI] [PubMed] [Google Scholar]
  10. Fauci A. S., Moutsopoulos H. M. Polyclonally triggered B cells in the peripheral blood and bone marrow of normal individuals and in patients with systemic lupus erythematosus and primary Sjögren's syndrome. Arthritis Rheum. 1981 Apr;24(4):577–583. doi: 10.1002/art.1780240402. [DOI] [PubMed] [Google Scholar]
  11. Fauci A. S., Steinberg A. D., Haynes B. F., Whalen G. Immunoregulatory aberrations in systemic lupus erythematosus. J Immunol. 1978 Oct;121(4):1473–1479. [PubMed] [Google Scholar]
  12. 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]
  13. Gronowicz E., Coutinho A., Melchers F. A plaque assay for all cells secreting Ig of a given type or class. Eur J Immunol. 1976 Aug;6(8):588–590. doi: 10.1002/eji.1830060812. [DOI] [PubMed] [Google Scholar]
  14. Horowitz S., Borcherding W., Moorthy A. V., Chesney R., Schulte-Wisserman H., Hong R. Induction of suppressor T cells in systemic lupus erythematosus by thymosin and cultured thymic epithelium. Science. 1977 Sep 2;197(4307):999–1001. doi: 10.1126/science.302032. [DOI] [PubMed] [Google Scholar]
  15. KUNKEL H. G., TAN E. M. AUTOANTIBODIES AND DISEASE. Adv Immunol. 1964;27:351–395. doi: 10.1016/s0065-2776(08)60711-7. [DOI] [PubMed] [Google Scholar]
  16. Kawanishi H., Saltzman L. E., Strober W. Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. I. T cells derived from Peyer's patches that switch sIgM B cells to sIgA B cells in vitro. J Exp Med. 1983 Feb 1;157(2):433–450. doi: 10.1084/jem.157.2.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kishimoto T., Miyake T., Nishizawa Y., Watanabe T., Yamamura Y. Triggering mechanism of B lymphocytes. I. Effect of anti-immunoglobulin and enhancing soluble factor on differentiation and proliferation of B cells. J Immunol. 1975 Nov;115(5):1179–1184. [PubMed] [Google Scholar]
  18. McKelvey E. M., Fahey J. L. Immunoglobulin changes in disease: quantitation on the basis of heavy polypeptide chains, IgG (gammaG), IgA (gammaA), and IgM (gammaM), and of light polypeptide chains, type K (I) and type L (II). J Clin Invest. 1965 Nov;44(11):1778–1787. doi: 10.1172/JCI105285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morimoto C., Reinherz E. L., Nadler L. M., Distaso J. A., Steinberg A. D., Schlossman S. F. Comparison in T- and B-cell markers in patients with Sjögren's syndrome and systemic lupus erythematosus. Clin Immunol Immunopathol. 1982 Feb;22(2):270–278. doi: 10.1016/0090-1229(82)90043-5. [DOI] [PubMed] [Google Scholar]
  20. Nies K. M., Stevens R. H., Louie J. S. Impaired immunoglobulin M synthesis by peripheral blood lymphocytes in systemic lupus erythematosus: a primary B-cell defect. Clin Immunol Immunopathol. 1981 Apr;19(1):118–130. doi: 10.1016/0090-1229(81)90053-2. [DOI] [PubMed] [Google Scholar]
  21. Nies K., Boyer R., Stevens R., Louie J. Anti-tetanus toxoid antibody synthesis after booster immunization in systemic lupus erythematosus. Comparison of the in vitro and in vivo responses. Arthritis Rheum. 1980 Dec;23(12):1343–1350. doi: 10.1002/art.1780231203. [DOI] [PubMed] [Google Scholar]
  22. Parker D. C., Wadsworth D. C., Schneider G. B. Activation of murine B lymphocytes by anti-immunoglobulin is an inductive signal leading to immunoglobulin secretion. J Exp Med. 1980 Jul 1;152(1):138–150. doi: 10.1084/jem.152.1.138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ralph P. Functional subsets of murine and human B lymphocyte cell lines. Immunol Rev. 1979;48:107–121. doi: 10.1111/j.1600-065x.1979.tb00300.x. [DOI] [PubMed] [Google Scholar]
  24. Rosner S., Ginzler E. M., Diamond H. S., Weiner M., Schlesinger M., Fries J. F., Wasner C., Medsger T. A., Jr, Ziegler G., Klippel J. H. A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death. Arthritis Rheum. 1982 Jun;25(6):612–617. doi: 10.1002/art.1780250602. [DOI] [PubMed] [Google Scholar]
  25. Sagawa A., Abdou N. I. Suppressor-cell dysfunction in systemic lupus erythematosus. Cells involved and in vitro correction. J Clin Invest. 1978 Oct;62(4):789–796. doi: 10.1172/JCI109190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saiki O., Kishimoto T., Kuritani T., Muraguchi A., Yamamura Y. In vitro induction of IgM secretion and switching to IgG production in human B leukemic cells with the help of T cells. J Immunol. 1980 Jun;124(6):2609–2614. [PubMed] [Google Scholar]
  27. Saiki O., Ralph P. Clonal differences in response to T cell replacing factor (TRF) for IgM secretion and TRF receptors in a human B lymphoblast cell line. Eur J Immunol. 1983 Jan;13(1):31–34. doi: 10.1002/eji.1830130108. [DOI] [PubMed] [Google Scholar]
  28. Saiki O., Ralph P., Cunningham-Rundles C., Good R. A. Three distinct stages of B-cell defects in common varied immunodeficiency. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6008–6012. doi: 10.1073/pnas.79.19.6008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Saiki O., Ralph P. Induction of human immunoglobulin secretion. I. Synergistic effect of B cell mitogen Cowan I plus T cell mitogens or factors. J Immunol. 1981 Sep;127(3):1044–1047. [PubMed] [Google Scholar]
  30. Saiki O., Ralph P. Induction of human immunoglobulin secretion. III. Inhibition of induction of IgG and IgA production in spleen but not peripheral blood cells by mitogenic antibody to IgM and IgD. Clin Immunol Immunopathol. 1982 Oct;25(1):114–125. doi: 10.1016/0090-1229(82)90170-2. [DOI] [PubMed] [Google Scholar]
  31. Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
  32. Tsokos G. C., Balow J. E. Spontaneous and pokeweed mitogen-induced plaque-forming cells in systemic lupus erythematosus. Clin Immunol Immunopathol. 1981 Nov;21(2):172–183. doi: 10.1016/0090-1229(81)90206-3. [DOI] [PubMed] [Google Scholar]
  33. Wallace D. J., Podell T., Weiner J., Klinenberg J. R., Forouzesh S., Dubois E. L. Systemic lupus erythematosus--survival patterns. Experience with 609 patients. JAMA. 1981 Mar 6;245(9):934–938. doi: 10.1001/jama.245.9.934. [DOI] [PubMed] [Google Scholar]

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