Abstract
Thein vitro production of IgA-anti-tetanus toxoid antibodies (IgA-Tet) by human peripheral blood lymphocytes (PBL) was assessed at various times afterin vivo intramuscular tetanus toxoid immunization. Five days after immunization, T cell- and mitogen-independent synthesis ofin vitro IgG-Tet, but not IgM-Tet or IgA-Tet, was detected. Two to six weeks after immunization, pokeweed mitogen (PWM)-stimulated cultures of B and T cells produced IgM-Tet and IgG-Tet but not IgA-Tet. We did, however, find that 75% of the serum samples of immunized individuals showed increases in IgA-Tet. Mitogen-dependentin vitro total IgA synthesis was detected in human PBL. Cells synthesizing the majority of PWM-induced IgA bear the phenotype Ig+ CR+ FcγR±. The majority of PPD-induced IgA synthesis was by cells lacking surface membrane IgD, similar to PPD-reactive IgG secretors. These results indicate that intramuscular immunization does not result in circulating B cells that can secrete antigen-specific IgA in mitogen-drivenin vitro cultures. Moreover, multiple B-cell subsets are responsible forin vitro IgA production.
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Montgomery PC, Connelly KM, Skandera CA: Remote-site stimulation of secretory IgA antibodies following bronchial and gastric stimulation.In Advances in Experimental Medicine and Biology, JR McGhee, J Mestecky, JL Babb (eds). New York, Plenum Press, 1978, Vol 107, pp 113–122
Mestecky J, McGhee RJ, Arnola RR, Michalek SM, Prince SJ, Babb JL: Selective induction of an immune response in human external secretions by ingestion of bacterial antigen. J Clin Invest 61:731–737, 1978
Ahlstedt S, Carlsson B, Fallstrom SP, Hanson LA, Holmgren J, Lidin-Janson G, Lindblad BS, Jodal U, Kaijser B, Sohl-Akerlund A, Wadsworth C: Antibodies in human serum and milk induced by enterobacteria and food proteins.In Immunology of the Gut, Ciba Foundation Symposium. New York, Elsevier Press, 1977, Vol 46, pp 115–134
Montgomery PC, Rosener BR, Cohn J: The secretory antibody response. Anti-DNP antibodies induced by dinitrophenylated type III pneumococcus. Immunol Commun 3:143–156, 1974
McDermott MR, Bienenstock J: Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory and genital tissues. J Immunol 122:1892–1898, 1979
McWilliams M, Philips-Quagliata JM, Lamm ME: Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis. J Exp Med 145:866–875, 1977
Wu LYF, Lawton AR, Cooper MD: Differentiation capacity of cultured B lymphocytes from immunodeficient patients. J Clin Invest 52:3180–3189, 1973
Lawton AR, Wu LYF, Cooper MD: The cellular basis of IgA deficiency in humans. Adv Exp Med Biol 45:373–380, 1974
Saxon A, Stevens RH, Ashman RF: Regulation of immunoglobulin production in human peripheral blood lymphocytes: Cellular interactions. J Immunol 118:1872–1879, 1977
Lethi RG, Brochier J: Human B cell differentiation. I. Immunoglobulin synthesis induced byNocardia mitogen. Eur J Immunol 8:119–123, 1978
Hammarstrom L, Bird AG, Smith CIE: Mitogenic activation of human lymphocytes: A protein A plaque assay evaluation of polyclonal B cell activators. Scand J Immunol 11:1–13, 1980
Saxon A, Stevens RH: Stimulation and regulation of human IgE production in vitro using peripheral blood lymphocytes. Clin Immunol Immunopathol 14:474–488, 1979
Pryjma J, Munoz J, Virella G, Fudenberg HH: Evaluation of IgM, IgG, IgD, and IgE secretion by human peripheral blood lymphocytes in cultures stimulated with pokeweed mitogen andStaphylococcus aureus Cowan I. Cell Immunol 50:115–124, 1980
Stevens RH, Saxon A: Control of antitetanus toxoid antibody production after booster immunization. J Clin Invest 62:1154–1160, 1978
Stevens RH, Saxon A: Differential synthesis of IgM and IgG antitetanus toxoid antibody in vitro following in vivo booster immunization of humans. Cell Immunol 45:142–150, 1979
Thiele CJ, Stevens RH: Antibody potential of human peripheral blood lymphocytes differentially expressing surface membrane IgM. J Immunol 124:1898–1904, 1980
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 122:2498–2504, 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
Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab 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
Miller RG, Phillips RA: Separation of cells by velocity sedimentation. J Cell Physiol 73:191–206, 1969
Stevens RH, Macy E, Thiele CJ: Evidence that pokeweed mitogen reactive B cells are pre-committed in vivo to the high rate secretion of a single immunoglobulin isotype in vitro. Scand J Immunol 14:449–457, 1982
Kuteh WH, Koopman WJ, Conley ME, Egan MF, Mestecky J: Production of predominantly polymeric IgA on human peripheral blood lymphocytes stimulated in vitro with mitogen. J Exp Med 152:1424–1429, 1981
Ogra PL, Karzon DT, Rightad F, MacGillivray M: Immunoglobulin response in serum and secretion after immunization with live and inactivated poliovaccine and natural infection. N Engl J Med 279:893–900, 1968
Yarchoan R, Murphy BR, Strober W, Clements ML, Nelson DL: In vitro production of anti-influenza virus antibody after intranasal inoculation with cold-adapted influenze virus. J Immunol 127:1958–1963, 1981
Pierce CW, Solliday SM, Asofsky R: Immune responses in vitro. IV. Suppression of primary γM, γG and γA plaque forming cell responses in mouse spleen cell cultures by class specific antibody to mouse immunoglobulin. J Exp Med 135:677–697, 1972
Cebra JJ, Craig SW, Jones PP: Cell types contributing to the biosynthesis of sIgA. Adv Exp Med Biol 45:23–33, 1974
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Thiele, C.J., Morrow, C.D. & Stevens, R.H. Human IgA antibody and immunoglobulin production afterin vivo tetanus toxoid immunization: Size and surface membrane phenotype analysis. J Clin Immunol 2, 327–334 (1982). https://doi.org/10.1007/BF00915075
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DOI: https://doi.org/10.1007/BF00915075