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Journal of Clinical Immunology

, Volume 4, Issue 4, pp 287–294 | Cite as

T-cell regulation of IgG subclass expression by mitogen-induced plasma cells: Soluble factors versus the T cells

  • M. Mayumi
  • T. Kuritani
  • M. D. Cooper
Original Articles

Abstract

The human IgG subclasses expressed by plasma cells generated from circulating B cells in response to soluble T-cell factors were examined by immunofluorescence using subclass-specific monoclonal antibodies. Soluble T-cell factors were induced by a mixed lymphocyte reaction, pokeweed mitogen (PWM), or phytohemagglutinin. The distribution of IgG subclasses expressed by plasma cells induced by these factors was IgG2> 5%, IgG1<25%, IgG3<1%, and IgG4<1%. On the other hand, IgG1 was dominant when B cells were cultured with T cells and PWM: IgG1 ∼70%, IgG2 ∼20%, IgG3 ∼8%, and IgG4 ∼1%. The addition of different amounts of the T-cell factors to B cells in culture did not alter the predominance of IgG2 plasma-cell differentiation. These results suggest that T cells and their soluble factors may preferentially enhance terminal differentiation of different IgG B-cell subpopulations. In contrast, the ratio of IgA1 to IgA2 plasma-cell responses was ∼1.5 to 1 regardless of whether the B-cell precursors were induced by T-cell factors or by the T cells plus PWM.

Key words

IgG surfaces regulation factors mitogens 

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References

  1. 1.
    Young WJ, Dorner MM, Kunkel HG, Kabat EA: Studies on human antibodies. VI. Selective variations in subgroup composition and genetic markers. J Exp Med 127:633–646, 1968Google Scholar
  2. 2.
    Riesen WF, Skvaril F, Broun DG: Natural infection of man with group A streptococci. Levels; restriction in class, subclass, and type; and clonal appearance of polysaccharide-group-specific antibodies. Scand J Immunol 5:383–390, 1976Google Scholar
  3. 3.
    Anderson U, Bird AG, Britton S, Palacios R: Humoral and cellular immunity in humans studied at the cell level from birth to two years of age. Immunol Rev 57:5–38, 1981Google Scholar
  4. 4.
    Morel A, Loghem EV, Nef M, Theilkaes L, Skvaril F: Determination of IgG subclasses and Gm allotypes in culture supernatants of pokeweed mitogen-stimulated human blood lymphocytes. J Immunol 121:566–572, 1981Google Scholar
  5. 5.
    Perlmutter RM, Hansburg D, Briles DE, Nicolotti RA, Davie JM: Subclass restriction of murine anti-carbohydrate antibodies. J Immunol 121:566–572, 1978Google Scholar
  6. 6.
    Slack J, der-Balian GP, Nahm M, Davie JM: Subclass restriction of murine antibodies. II. The IgG plaque-forming cell response to thymus-independent Type 1 and Type 2 antigens in normal mice and mice expressing an X-linked immunodeficiency. J Exp Med 151:853–862, 1980Google Scholar
  7. 7.
    Lowy I, Theze J, Chedid L: Stimulation of thein vivo dinitrophenyl antibody response to the DNP conjugate of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) polymer by a synthetic adjuvant, muramyl dipeptide (MDP): Target cells from adjuvant activity and isotypic pattern of MDP-stimulated response. J Immunol 124:100–104, 1980Google Scholar
  8. 8.
    Torrigiani G: Quantitative estimation of antibody in the immunoglobulin classes of the mouse. II. Thymic dependence of the different classes. J Immunol 108:161–164, 1972Google Scholar
  9. 9.
    Kearney JF, Klein J, Bockman DE, Cooper MD, Lawton AR: B cell differentiation induced by lipopolysaccharide. V. Suppression of plasma cell maturation by anti-μ: Mode of action and characteristics of suppressed cells. J Immunol 120:158–166, 1978Google Scholar
  10. 10.
    Augustin AA, Coutinho A: Specific T helper cells that activate B cells polyclonally.In vitro enrichment and cooperative function. J Exp Med 151:587–601, 1980Google Scholar
  11. 11.
    Martinez-AC, Coutinho A, Augustin AA: Immunoglobulin C-gene expression. I. The commitment of IgG subclass of secretory cells is determined by the quality of the nonspecific stimuli. Eur J Immunol 10:698–702, 1980Google Scholar
  12. 12.
    Mongini PKA, Stein KE, Paul WE: T cell regulation of IgG subclass antibody production in response to T-independent antigens. J Exp Med 153:1–12, 1981Google Scholar
  13. 13.
    Mongini PKA, Paul WE, Metcalf ES: T cell regulation of immunoglobulin class expression in the antibody response to trinitrophenyl-ficoll. Evidence for T cell enhancement of the immunoglobulin class switch. J Exp Med 155:884–902, 1982Google Scholar
  14. 14.
    Seman M, Zilberfarb V: Genetic control of the IgG2a response to sheep erythrocytes in mice: Isotype- and antigen-specific T cell-mediated suppression in low responders. J Immunol 122:2534–2540, 1979Google Scholar
  15. 15.
    Lowy I, Joskowicz M, Theze J: Characterization of suppressor cells regulatingin vitro expression of IgG2a and IgG2b antibody responses. J Immunol 128:768–773, 1982Google Scholar
  16. 16.
    Isakson PC, Pure E, Vitetta ES, Krammer PH: T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med 155:734–748, 1982Google Scholar
  17. 17.
    Coutinho A, Pettersson S, Ruuth E, Forni L: Immunoglobulin C gene expression. IV. Alternate control of IgG1-producing cells by helper cell-derived B cell-specific growth or maturation factors. Eur J Immunol 13:269–272, 1983Google Scholar
  18. 18.
    Mayumi M, Kuritani T, Kubagawa H, Cooper MD: IgG subclass expression by human B lymphocytes and plasma cells: B lymphocytes precommitted to IgG subclass can be preferentially induced by polyclonal mitogens with T cell help. J Immunol 130:671–677, 1983Google Scholar
  19. 19.
    Melchers F, Andersson J, Lernhardt W, Schreier MH: Roles of surface-bound immunoglobulin molecules in regulating the replication and maturation to immunoglobulin secretion of B lymphocytes. Immunol Rev 52:89–114, 1980Google Scholar
  20. 20.
    Schimpl A, Wecker E: A third signal in B cell activation given by TRE. Transplant Rev 23:176–188, 1975Google Scholar
  21. 21.
    Julius MH, von Boehmer H, Sidman CL: Dissociation of two signals required for activation of resting B cells. Proc Natl Acad Sci USA 79:1989–1993, 1982Google Scholar
  22. 22.
    Andersson J, Melcher F: T cell dependent activation of resting B cells: Requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors. Proc Natl Acad Sci USA 78:2497–2501, 1981Google Scholar
  23. 23.
    Watson J, Gillis S, Marbrook J, Mochizuki D, Smith KA: Biochemical and biological characterization of lymphocyte regulatory molecules. I. Purification of a class of murine lymphokines. J Exp Med 150:849–861, 1979Google Scholar
  24. 24.
    Chiorazzi N, Fu SM, Kunkel HG: Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors. J Exp Med 149:1543–1548, 1979Google Scholar
  25. 25.
    Muraguchi A, Butler JL, Kehrl JH, Fauci AS: Differential sensitivity of human B cell subsets to activation signals delivered by anti-μ antibody and proliferative signals delivered by a monoclonal B cell growth factor. J Exp Med 157:530–546, 1983Google Scholar
  26. 26.
    Boyum A: Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 21 (Suppl 97):77–82, 1968Google Scholar
  27. 27.
    Lowe J, Bird P, Hardie D, Jefferis R, Ling NR: Monoclonal antibodies to determinants on human γ chains: Properties of antibodies showing subclass restriction of subclass specificity. Immunology 47:329–336, 1982Google Scholar
  28. 28.
    Conley ME, Kearney JF, Lawton AR III, Cooper MD: Differentiation of human B cells expressing the IgA subclass as demonstrated by monoclonal hybridoma antibodies. J Immunol 125:2311–2316, 1980Google Scholar
  29. 29.
    Gathings WE, Lawton AR, Cooper MD: Immunofluorescent studies of the development of pre-B cells, B lymphocytes and immunoglobulin isotype diversity in humans. Eur J Immunol 7:804–810, 1977Google Scholar
  30. 30.
    Pellegrino MA, Ferrone S, Dierich MP, Reisfeld RA: Enhancement of sheep red blood cell human lymphocyte rosette formation by the sulfhydryl compound 2-aminoethylisothiouronium bromide. Clin Immunol Immunopathol 23:324–334, 1975Google Scholar
  31. 31.
    Hanjan SNS, Kearney JF, Cooper MD: A monoclonal antibody (MMA) that identifies a differentiation antigen on human myelomonocytic cells. Clin Immunol Immunopathol 23:172–188, 1982Google Scholar
  32. 32.
    Gillis S, Smith KA, Watson J: Biochemical characterization of lymphocyte regulatory molecules. II. Purification of a class of rat and human lymphokines. J Immunol 124:1954–1962, 1980Google Scholar
  33. 33.
    Mayumi M, Kubagawa H, Omura GA, Gathings WE, Kearney JF, Cooper MD: Studies on the clonal origin of human B cell leukemia using monoclonal anti-idiotype antibodies. J Immunol 129:904–910, 1982Google Scholar
  34. 34.
    Janossy G, Greaves M: Functional analysis of murine and human B lymphocyte subsets. Transplant Rev 24:177–236, 1975Google Scholar
  35. 35.
    Kuritani T, Cooper MD: Human B cell differentiation. II. Pokeweed mitogen-responsive B cells belong to a surface immunoglobulin D-negative subpopulation. J Exp Med 155:1561–1566, 1982Google Scholar
  36. 36.
    Dagg MK, Levitt D: Human B-lymphocyte subpopulations. I. Differentiation of density-separated B lymphocytes. Clin Immunol Immunopathol 21:39–49, 1981Google Scholar
  37. 37.
    Levitt D, Dagg MK: Human B-lymphocyte subpopulations. II. Plasma cell differentiation of isotype-specific B lymphocytes from peripheral blood. Clin Immunol Immunopathol 21:50–76, 1981Google Scholar
  38. 38.
    Lucivero G, Lawton AR, Cooper MD: Rosette formation with mouse erythrocytes defines a population of human B lymphocytes unresponsive to pokeweed mitogen. Clin Exp Immunol 45:185–190, 1981Google Scholar
  39. 39.
    Finlay GJ, Booth RJ, Marbrook J: Antibody responses of human lymphocytesin vitro. Specificity and physical properties of plaque-forming cell precursors. Aust J Exp Biol Med Sci 57:587–596, 1979Google Scholar
  40. 40.
    Lucivero G, Lawton AR, Cooper MD: Pokeweed mitogen-induced differentiation of human blood B lymphocytes. II. Suppression of plasma cell differentiation by heavy chain specific antibodies and development of immunoglobulin class restriction. Hum Lymphocyte Different 1:27–36, 1981Google Scholar
  41. 41.
    Kuritani T, Cooper MD: Human B cell differentiation. I. Analysis of immunoglobulin heavy chain switching using monoclonal anti-immunoglobulin M, G, and A antibodies and pokeweed mitogen-induced plasma cell differentiation. J Exp Med 155:839–851, 1982Google Scholar
  42. 42.
    Stevens RH, Macy E, Thiele CJ: Evidence that pokeweed mitogen reactive B-cells are precommittedin vivo to the high rate secretion of a single immunoglobulin isotypein vitro. Scand J Immunol 14:449–457, 1981Google Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • M. Mayumi
    • 1
  • T. Kuritani
    • 1
  • M. D. Cooper
    • 1
  1. 1.The Cellular Immunobiology Unit of the Tumor Institute, Department of Pediatrics and Microbiology, and The Comprehensive Cancer CenterUniversity of Alabama in BirminghamBirmingham

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