Abstract
The B lymphocyte subpopulations producing immunoglobulin (Ig)E and the regulatory T cells modulating this IgE production in normals, and in atopic patients with respiratory allergy, atopic dermatitis, and markedly elevated serum IgE levels (>5,000 ng/ml), were investigated. Peripheral blood lymphocytes (PBL) were separated into T and B cell fractions and the ability of B cells to produce IgE in the presence or absence of pokeweed mitogen (PWM) and/or T cells ws determined. The patients had a circulating population of cells which spontaneously produced up to 6 ng of IgE in vitro (per 4 X 10(5) non-E-rosetting cells) in the absence of T lymphocytes and PWM. PBL from normals did not possess such cells. This IgE synthesis occurred primarily (>75%) over the first 72 h of culture. There was a wide range in their activity between patients and from the same patient studied on repeated occasions (from <300 to 6,000 pg per culture). This spontaneous IgE production was inhibited by PWM (mean inhibition, 37%) or normal T lymphocytes (mean inhibition, 42%). The patients lacked T lymphocytes capable of inhibiting this spontaneous IgE synthesis in 7 of 13 experiments. Functionally distinct B cells were identified in the patients and normals that responded to PWM with IgE production in vitro and required T-helper cell activity. Patients had normal PWM-responsive B cell IgE biosynthetic activity and T-helper function for these B cells. Suppressor T cell activity for PWM-driven IgE synthesis was also evaluated. Both the normals' and the patients' T lymphocytes provided similar levels of T cell suppressor function for PWM-driven IgE production. Patients with elevated serum IgE possessed these inhibitory T cells at times when the T lymphocytes which suppressed spontaneous igE production were absent from their PBL.
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- Buckley R. H., Becker W. G. Abnormalities in the regulation of human IgE synthesis. Immunol Rev. 1978;41:288–314. doi: 10.1111/j.1600-065x.1978.tb01469.x. [DOI] [PubMed] [Google Scholar]
- Buckley R. H., Wray B. B., Belmaker E. Z. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection. Pediatrics. 1972 Jan;49(1):59–70. [PubMed] [Google Scholar]
- 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]
- Eby W. C., Chong C. A., Dray S., Molinaro G. A. Enumerating immunoglobulin-secreting cells among peripheral human lymphocytes. A hemolytic plaque assay for a B cell function. J Immunol. 1975 Dec;115(6):1700–1703. [PubMed] [Google Scholar]
- Fiser P. M., Buckley R. H. Human IgE biosynthesis in vitro: studies with atopic and normal blood mononuclear cells and subpopulations. J Immunol. 1979 Oct;123(4):1788–1794. [PubMed] [Google Scholar]
- Frost H., Braun D. G., Poskitt D., Cahill R. N., Trnka Z. Antipolysaccharide antibodies of restricted heterogeneity secreted by a single lymph node. J Exp Med. 1976 Mar 1;143(3):707–711. doi: 10.1084/jem.143.3.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geha R. S., Hyslop N., Alami S., Farah F., Schneeberger E. E., Rosen F. S. Hyper immunoglobulin M immunodeficiency. (Dysgammaglobulinemia). Presence of immunoglobulin M-secreting plasmacytoid cells in peripheral blood and failure of immunoglobulin M-immunoglobulin G switch in B-cell differentiation. J Clin Invest. 1979 Aug;64(2):385–391. doi: 10.1172/JCI109473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Gonzalez-Molina A., Spiegelberg H. L. A subpopulation of normal human peripheral B lymphcytes that bind IgE. J Clin Invest. 1977 Apr;59(4):616–624. doi: 10.1172/JCI108679. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hill S. W. Distribution of plaque-forming cells in the mouse for a protein antigen. Evidence for highly active parathymic lymph nodes following intraperitoneal injection of hen lysozyme. Immunology. 1976 Jun;30(6):895–906. [PMC free article] [PubMed] [Google Scholar]
- Ishizaka K. Cellular events in the IgE antibody response. Adv Immunol. 1976;23:1–75. doi: 10.1016/s0065-2776(08)60318-1. [DOI] [PubMed] [Google Scholar]
- Ishizaka K., Ishizaka T., Lee E. H. Biologic function of the Fc fragments of E myeloma protein. Immunochemistry. 1970 Aug;7(8):687–702. doi: 10.1016/0019-2791(70)90175-8. [DOI] [PubMed] [Google Scholar]
- Ishizaka T., Ishizaka K. Biology of immunoglobulin E. Molecular basis of reaginic hypersensitivity. Prog Allergy. 1975;19:60–121. [PubMed] [Google Scholar]
- Jarrett E. E. Stimuli for the production and control of IgE in rats. Immunol Rev. 1978;41:52–76. doi: 10.1111/j.1600-065x.1978.tb01460.x. [DOI] [PubMed] [Google Scholar]
- Lawrence E. C., Blaese R. M., Martin R. R., Stevens P. M. Immunoglobulin secreting cells in normal human bronchial lavage fluids. J Clin Invest. 1978 Oct;62(4):832–835. doi: 10.1172/JCI109195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller R. G., Phillips R. A. Separation of cells by velocity sedimentation. J Cell Physiol. 1969 Jun;73(3):191–201. doi: 10.1002/jcp.1040730305. [DOI] [PubMed] [Google Scholar]
- Ogawa M., Kochwa S., Smith C., Ishizaka K., McIntyre O. R. Clinical aspects of IgE myeloma. N Engl J Med. 1969 Nov 27;281(22):1217–1220. doi: 10.1056/NEJM196911272812204. [DOI] [PubMed] [Google Scholar]
- Patterson R., Suszko I. M., Metzger W. J., Roberts M. In vitro production of IgE by human peripheral blood lymphocytes: effect of cholera toxin and beta adrenergic stimulation. J Immunol. 1976 Jul;117(1):97–101. [PubMed] [Google Scholar]
- Rosenberg S. A., Lipsky P. E. Monocyte dependence of pokeweed mitogen-induced differentiation of immunoglobulin-secreting cells from human peripheral blood mononuclear cells. J Immunol. 1979 Mar;122(3):926–931. [PubMed] [Google Scholar]
- Saxon A., Feldhaus J., Robins R. A. Single step separation of human T and B cells using AET treated srbc rosettes. J Immunol Methods. 1976;12(3-4):285–288. doi: 10.1016/0022-1759(76)90050-8. [DOI] [PubMed] [Google Scholar]
- Saxon A., Portis J. Lymphoid subpopulation changes in regional lymph nodes in squamous head and neck cancer. Cancer Res. 1977 Apr;37(4):1154–1158. [PubMed] [Google Scholar]
- Saxon A., Stevens R. H. Stimulation and regulation of human IgE production in vitro using peripheral blood lymphocytes. Clin Immunol Immunopathol. 1979 Dec;14(4):474–488. doi: 10.1016/0090-1229(79)90100-4. [DOI] [PubMed] [Google Scholar]
- Saxon A., Stevens R. H. Suppression of immunoglobulin production in normal human blood: characterization of the cells responsible and mediation by a soluble T lymphocyte-derived factor. Clin Immunol Immunopathol. 1978 Aug;10(4):427–437. doi: 10.1016/0090-1229(78)90155-1. [DOI] [PubMed] [Google Scholar]
- 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]
- Sorkin E., Landy M. Antibody production by blood leucocytes. Experientia. 1965 Nov 15;21(11):677–680. doi: 10.1007/BF02144077. [DOI] [PubMed] [Google Scholar]
- Stevens R. H., Macy E., Morrow C., Saxon A. Characterization of a circulating subpopulation of spontaneous antitetanus toxoid antibody producing B cells following in vivo booster immunization. J Immunol. 1979 Jun;122(6):2498–2504. [PubMed] [Google Scholar]
- Stevens R. H., Saxon A. Differential synthesis of IgM and IgA anti-tetanus toxoid antibody in vitro following in vivo booster immunization of humans. Cell Immunol. 1979 Jun;45(1):142–150. doi: 10.1016/0008-8749(79)90369-1. [DOI] [PubMed] [Google Scholar]
- Stevens R. H., Saxon A. Immunoregulation in humans: control of antitetanus toxoid antibody production after booster immunization. J Clin Invest. 1978 Dec;62(6):1154–1160. doi: 10.1172/JCI109234. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T. Regulation of reaginic antibody formation in animals. Prog Allergy. 1975;19:122–194. [PubMed] [Google Scholar]
- 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]
- Tjio A. H., Hull W. M., Gleich G. J. Production of human immunoglobulin E antibody in vitro. J Immunol. 1979 May;122(5):2131–2133. [PubMed] [Google Scholar]
- Waldmann T. A., Blaese R. M., Broder S., Krakauer R. S. Disorders of suppressor immunoregulatory cells in the pathogenesis of immunodeficiency and autoimmunity. Ann Intern Med. 1978 Feb;88(2):226–238. doi: 10.7326/0003-4819-88-2-226. [DOI] [PubMed] [Google Scholar]
- Yodoi J., Ishizaka K. Lymphocytes bearing Fc receptors for IgE. I. Presence of human and rat T lymphocytes with Fc epsilon receptors. J Immunol. 1979 Jun;122(6):2577–2583. [PubMed] [Google Scholar]
- Zollinger W. D., Dalrymple J. M., Artenstein M. S. Analysis of parameters affecting the solid phase radioimmunoassay quantitation of antibody to meningococcal antigens. J Immunol. 1976 Nov;117(5 PT2):1788–1798. [PubMed] [Google Scholar]