Abstract
Tetanus toxoid (Tet) booster immunization induces the transient appearance in the circulation of lymphoblastoid (LB) B cells which spontaneously produce anti-tetanus toxoid IgG antibody (IgG-Tet) during a 3-dayin vitro culture. In this study we have examined the effects of TPA on the ability of LB cells to secrete antibody and have found that as little as 10 ng/ml of TPA provoked a marked inhibition of the induced LB cells' IgG-Tet production. This inhibitory effect was observed only when TPA was added early in the culture and could be achieved by pretreating the B cells with TPA for as little as 1 hr. Only marginal inhibition of IgG-Tet production was observed if the addition of TPA was delayed 14–24 hr. The TPA inhibition was not mediated by contaminant T cells as the addition of increasing numbers of T cells to LB cell cultures proportionally reversed the TPA inhibitory effect. Likewise, the inhibition of antibody synthesis was not due to a monocyte-dependent mechanism since (1) substantial depletion of adherent cells did not reverse the inhibition of antibody synthesis, (2) the addition of a monocyte-enriched population to monocyte-depleted B cells did not enhance, but in fact partially reversed, the inhibition caused by TPA, and (3) the addition of monocyte populations pretreated with TPA to monocyte-depleted B-cell fractions did not inhibit subsequent IgG-Tet production by the LB cells.
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References
Van Duuren BL: Tumor promoting agents in two-stage carcinogenesis. Prog Exp Tumor Res 11:31–68, 1969
Hecker E: Isolation and characterization of the cocarcinogenic principles from croton oil. Methods Cancer Res 6:439–444, 1971
Lotem J, Sachs L: Regulation of normal differentiation in mouse and human myeloid leukemic cells by phorbol esters and the mechanism of tumor promotion. Proc Natl Acad Sci 76:5158–5162, 1979
Rovera G, Santoli D, Damsky C: Human promyelocytyc leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci 76:2779–2783, 1979
Touraine JL, Hadden J, Touraine F, Hadden EM, Estensen RD, Good RA: Phorbol myristate acetate: A mitogen selective for a T-lymphocyte subpopulation. J Exp Med 145:460–465, 1977
Driedger PA, Blumberg PM: The effect of phorbol diesters on chicken embryo fibroblasts. Cancer Res 37:3257–3265, 1977
Weinstein BI, Lee LS, Fisher PB, Mufson A, Yamasaki H: Action of phorbol esters in cell culture: Mimicry of transformation, altered differentiation and effects on cell membranes. J Supramol Struct 12:195–208, 1979
Kolata G: Clues to cell growth and differentiation. Science 220:291–292, 1983
Sando JJ, Hilfiker DS, Salomon DK, Farrar JJ: Specific receptors for phorbol esters in lymphoid cell populations: role in enhanced production of T-cell growth factor. Proc Natl Acad Sci 78:1189–1191, 1981
Abb J, Bayliss GK, Deinhardt F: Lymphocyte activation by the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate TPA. J Immunol 122:1639–1642, 1979
Stadler BM, Dougherty SF, Farrar DS, Farrar JJ: Relationship of cell cycle to recovery of IL-2 activity from human mononuclear cells, human and mouse T cell lines. J Immunol 127:1936–1940, 1981
Solbach W: Tumor-promoting phorbol esters selectively abrogate the expression of the T4 differentiation antigen expressed on normal and malignant T helper lymphocytes. J Exp Med 156:1250–1255, 1982
Nagasawa K, Chechik BE, Gelfand EW, Sengupta S, Letarte M, Mak TW: Modulation of Hu T-cell differentiation markers by 12-O-tetradecanoylphorbol-13-acetate. Thymus 3:307–311, 1981.
Ralph P, Kishimoto T: Tumor-promoting phorbol myristic acetate stimulates Ig secretion correlated with growth cessation in human B lymphocyte cell lines. J Clin Invest 68:1093–1100, 1981
Nowell P, Shankey TV, Finan J, Guerry D, Besa E: Proliferation, differentiation and cytogenetics of chronic leukemic lymphocytes cultured with mitomycin-treated normal cells. Blood 57:444–450, 1981
Totterman JH, Nilsson K, Sundstrom C: Phorbol ester-induced differentiation of chronic lymphocyte leukemia cells. Nature 288:176–178, 1980
Stevens RH, Saxon A: Immunoregulation in humans: Control of anti-tetanus toxoid antibody production after booster immunization. J Clin Invest 62:1154–1160, 1979
Stevens RH, Saxon A: Differential synthesis of IgM and IgG antitetanus toxoid antibody in vitro following in vivo booster immunization. Cell Immunol 54:142–150, 1979
Stevens RH, 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 122:2498–2503, 1979
Thiele CJ, Morrow CD, Stevens RH: Multiple subsets of antitetanus toxoid antibody producing cells in human peripheral blood differ by size, expression of membrane receptors and mitogen reactivity. J Immunol 126: 1146–1153, 1981
Thomson PD, Harris NS: Detection of plaque forming cells in the peripheral blood of actively immunized humans. J Immunol 118:1480–1482, 1977
Yarchoan R, Murphy BR, Strober W, Clements ML, Nelson DL: In vitro production of anti-influenza antibody after intranasal inoculation with cold-adapted influenza virus. J Immunol 127:1958–1963, 1981
Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Invest 21:77–108, 1968
Saxon A, Feldhaus JL, Robbins RA: Single step separation of human T and B cells using AET-treated SRBC rosettes. J Immunol Methods 12:285–289, 1976
Sanderson RJ, Shepperdson FT, Vatter AE, Talmage DW: Isolation and enumeration of peripheral blood monocytes. J Immunol 118:1409–1414, 1977
Nies KM, Stevens RH, Louie JS: Impaired immunoglobulin M synthesis by peripheral blood lymphocytes in SLE. Clin Immunol Immunopathol 19:118–130, 1981
Tucker SB, Pierre EV, Jordon RE: Rapid identification of monocytes in a mixed mononuclear cell preparation. J Immunol Methods 14:267–270, 1977
Brieva J, Stevens RH: Inhibition of human antigen-induced lymphoblastoid B cell function by an in vivo-induced suppressor T cell. Cell Immunol 77:109–119, 1983
Mizel SB, Rosenstriech DL, Oppenheim JJ: Phorbol myristic acetate stimulates LAF production by the macrophage cell line P388D. Cell Immunol 40:230–235, 1978
Wright SD, Silverstein SC: Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med 156:1149–1164, 1982
Sugawara I: The immunoglobulin production of human peripheral B lymphocytes induced by phorbol myristate acetate. Cell Immunol 72:88–96, 1982
Jagielski P, Gregg SL, Gajl-Peczalska KJ: TPA, tumor promoter-induced suppression of immunoglobulin secretion in human blood lymphocytes. J Immunol 130:1159–1163, 1983
Roth P, Halper JP, Weinstein B, Pernis B: A phorbol ester tumor promoter induces changes in the expression of immunoglobulins and DR antigens in human lymphoblastoid cells. J Immunol 129:539–544, 1982
Ginsburg WW, Finkelman FD, Lipsky PE: Circulating and pokeweed mitogen-induced immunoglobulin secreting cells in systemic lupus erythematosus. Clin Exp Immunol 35:76–88, 1979
Cohen R, Pacifici M, Rubinstein N, Biehl J, Holtzer H: Effect of a tumour promoter on myogenesis. Nature 266:538–540, 1977
Rovera G, O'Brien T, Diamond L: Tumor promoters inhibit spontaneous differentiation of Friend erythroleukemia cells in culture. Proc Natl Acad Sci 74:2894–2898, 1977
Kasukabe T, Honma Y, Hozumi M: Inhibition of functional and morphological differentiation of cultured mouse myeloid leukemia cells by tumor promoters. Gann 70:119–123, 1979
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Brieva, J.A., Louie, J.S. & Stevens, R.H. 12-O-tetradecanoylphorbol-13-acetata (TPA) directly inhibits spontaneous immunoglobulin secretion byin vivo antigen-induced human lymphoblastoid B cells. J Clin Immunol 4, 280–286 (1984). https://doi.org/10.1007/BF00915295
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DOI: https://doi.org/10.1007/BF00915295