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Lipopolysaccharides: From Immunostimulation to Autoimmunity

  • Chapter
Immunostimulation

Abstract

Lipopolysaccharides (LPS) from gram-negative bacteria have a variety of effects on mammalian cells; their mitogenic activity on bone-marrow derived (B) lymphocytes represents the best characterized biological effect of LPS on cells involved in the immune response [30, 32]. LPS have been identified as powerful adjuvants in antibody responses [11, 23], although under certain circumstances LPS can suppress such responses [35]. LPS are also potent immunogens in vivo since extremely low doses are sufficient to induce a specific antibody response [57, 64]. Furthermore, the triggering by LPS of antibodies with specificities for some self-antigens has been demonstrated [25, 28, 62]. In this review we will first describe briefly some biologic effects of LPS on the immune system and particular emphasis will be placed on the discussion of the possible cellular basis of these effects of LPS. The second part will be mainly concerned with the analysis of the mechanisms involved in the formation of auto-antibodies after injection of LPS in mice. Indeed, LPS can induce immunopathologic manifestations which suggest that immunostimulation may occasionally lead to the development of various features of autoimmune diseases.

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References

  1. Allison, A. C., Davies, A. T. S.: Requirements of thymus-dependent lymphocytes for potentiation by adjuvants of antibody formation. Nature 233, 330 (1972)

    Article  Google Scholar 

  2. Amerding, D., Katz, D. H.: Activation of T and B lymphocytes in vitro. I. Regulatory influence of bacterial lipopolysaccharide (LPS) on specific T cell helper function. J. Exp. Med. 139, 24 (1974)

    Article  Google Scholar 

  3. Andersson, J., Möller, G., Sjoberg, O.: Selective induction of DNA synthesis in T and B lymphocytes. Cell. Immunol. 4, 381 (1972)

    Article  PubMed  CAS  Google Scholar 

  4. Andersson, J., Sjoberg, O., Möller, S.: Mitogens as probes for immunocyte activation and cellular cooperation. Transplant. Rev. 11, 131 (1972)

    PubMed  CAS  Google Scholar 

  5. Andersson, J., Sjoberg, O., Möller, G.: Induction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides. Eur. J. Immunol. 2, 349 (1972)

    Article  PubMed  CAS  Google Scholar 

  6. Andersson, J., Melchers, F., Galanos, G., Lüderitz, O.: The mitogenic effect of lipopolysaccharide on bone-marrow-derived mouse lymphocytes. Lipid A as the mitogenic part of the molecule. J. Exp. Med. 137, 943 (1973)

    Article  PubMed  CAS  Google Scholar 

  7. Andersson, J., Bullock, W. W., Melchers, F.: Inhibition of mitogenic stimulation of mouse lymphocytes by anti-mouse immunoglobulin antibodies. I. Mode of action. Eur. J. Immunol. 4, 715 (1974)

    CAS  Google Scholar 

  8. Andersson, J., Coutinho, A., Melchers, F.: Frequencies of mitogen-reactive B cells in the mouse. I. Distribution in different lymphoid organs from different inbred strains of mice at different ages. J. Exp. Med. 145, 1511 (1977)

    Article  PubMed  CAS  Google Scholar 

  9. Andersson, J., Coutinho, A., Melchers, F.: Stimulation of murine B lymphocytes to IgG synthesis and secretion by the mitogens lipopolysaccharide and lipoprotein and its inhibition by anti-immunoglobulin antibodies. Eur. J. Immunol. 8, 336 (1978)

    Article  PubMed  CAS  Google Scholar 

  10. Andersson, J., Coutinho, A., Melchers, F.: The switch from IgM to IgG secretion in single mitogen-stimulated B cell clones. J. Exp. Med. 147, 1744 (1978)

    Article  PubMed  CAS  Google Scholar 

  11. Bullock, W. W., Andersson, J.: Mitogens as probes for immunocyte activation: specific and nonspecific paralysis of B cell mitogenesis. In: Ciba Foundation Symposium 18, p. 173. Amsterdam: Elsevier 1973

    Chapter  Google Scholar 

  12. Chiller, J. M., Skidmore, B. J., Morrison, D. C., Weigle, W. O.: Relationship of the structure of bacterial lipopolysaccharides to its function in mitogenesis and adjuvanticity. Proc. Nat. Acad. Sci. USA 70, 2129 (1973)

    Article  PubMed  CAS  Google Scholar 

  13. Chiller, J. M., Weigle, W. O.: Termination of tolerance to human gammaglobulin in mice by antigen and bacterial lipopolysaccharide (endotoxin). J. Exp. Med. 137, 740 (1973)

    Article  PubMed  CAS  Google Scholar 

  14. Chiller, J. M., Louis, J. A., Skidmore, B. J., Weigle, W. O.: Cellular parameters of the tolerant state induced to human γ globulin in mice and of its modulation by bacterial lipopolysaccharides. In: Immunological tolerance Katz, D. H., Benacerraf, B., Eds. p. 373. New York: Academic Press 1974

    Google Scholar 

  15. Chiller, J. M., Louis, J. A., Skidmore, B. J., Weigle, W. O.: Manipulation of a tolerant state: cells and signals. In: The immune system, genes, receptors, signals Sercarz, E., Williamson, A., Fox, C., p. 553. eds. New York: Academic Press 1974

    Google Scholar 

  16. Claman, H. N.: Tolerance to a protein antigen in adult mice and the effect of non-specific factors. J. Immunol. 91, 833 (1963)

    PubMed  CAS  Google Scholar 

  17. Coutinho, A., Gronowicz, E., Bullock, W. W., Möller, G.: Mechanism of thymus-independent immunocyte triggering. J. Exp. Med. 139, 74 (1974)

    Article  PubMed  CAS  Google Scholar 

  18. Coutinho, A., Möller, G.: Immune activation of B cells: Evidence for ‘one non-specific triggering signal’ not delivered by the Ig receptors. Scand. J. Immunol. 3, 133 (1974)

    Article  PubMed  CAS  Google Scholar 

  19. Coutinho, A., Möller, G.: Thymus-independent B-cell induction and paralysis. Adv. Immunol. 21, 113 (1975)

    Article  PubMed  CAS  Google Scholar 

  20. Coutinho, A., Forni, L., Wetanabe, T.: Genetic and functional characterization of an antiserum to the Lipid A-specific triggering receptor on murine B lymphocytes. Eur. J. Immunol. 8, 63 (1978)

    Article  PubMed  CAS  Google Scholar 

  21. Diamantstein, T., Keppler, W., Blitstein-Willinger, E., Ben-Efraim, S.: Suppression of the primary immune response in vivo to sheep red blood cells by B cell mitogens. Immunology, 30, 401 (1976)

    PubMed  CAS  Google Scholar 

  22. Dresser, D. W.: Effectiveness of lipid and lipidophilic substances as adjuvants. Nature 191, 1169 (1961)

    Article  PubMed  CAS  Google Scholar 

  23. Dresser, D. W., Phillips, J. M.: The cellular targets for the action of adjuvants: T-adjuvants and B-adjuvants. In: Ciba Foundation Symposium 18. p. 3. Amsterdam: Elsevier 1973

    Chapter  Google Scholar 

  24. Dresser, D. W., Popham, A. M.: Induction of an IgM anti-(bovine)-IgG response in mice by bacterial lipopolysaccharide. Nature 264, 552 (1976)

    Article  PubMed  CAS  Google Scholar 

  25. Esquivel, P. S., Rose, N. R., Kong, Y. M.: Induction of autoimmunity in good and poor responder mice with mouse thyroglobulin and lipopolysaccharide. J. Exp. Med. 145, 1250 (1977)

    Article  PubMed  CAS  Google Scholar 

  26. Fidler, J. M.: In vivo immune response to TNP hapten coupled to thymus-independent carrier lipopolysaccharide. Cell. Immunol. 16, 223 (1975)

    Article  PubMed  CAS  Google Scholar 

  27. Eorni, L., Coutinho, A.: An antiserum which recognizes lipopolysaccharide-reactive B cells in the mouse. Eur. J. Immunol. 8, 56 (1978)

    Article  Google Scholar 

  28. Fournié, G. J., Lambert, P. H., Miescher, P. A.: Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J. Exp. Med. 140, 1189 (1974)

    Article  PubMed  Google Scholar 

  29. Franzl, R. E., McMaster, P. D.: The primary immune response in mice. I. The enhancement and suppression of hemolysin production by a bacterial endotoxin. J. Exp. Med. 127, 1087 (1968)

    Article  PubMed  CAS  Google Scholar 

  30. Gery, I., Krüger, K., Spiegel, S. Z.: Stimulation of B lymphocytes by endotoxin. Reactions of thymus-deprived mice and karyolytic analysis of dividing cells in mice bearing T6 T6 thymus grafts. J. Immunol. 108, 1088 (1972)

    PubMed  CAS  Google Scholar 

  31. Gery, I., Waksman, B. H.: Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediators. J. Exp. Med. 136, 143 (1972)

    Article  PubMed  CAS  Google Scholar 

  32. Greaves, M. F., Janossy, G.: Elicitation of selective T and B lymphocyte responses by cell surface binding ligands. Transplant. Rev. 11, 87 (1972)

    PubMed  CAS  Google Scholar 

  33. Greaves, M., Janossy, G., Doenhoff, M.: Selective triggering of human T and B lymphocytes in vitro by polyclonal mitogens. J. Exp. Med. 140, 2 (1974)

    Article  Google Scholar 

  34. Hamaoka, T., Katz, D. H.: Cellular site of action of various adjuvants in antibody responses to hapten-carrier conjugates. J. Immunol. 111, 1554 (1973)

    PubMed  CAS  Google Scholar 

  35. Hoffmann, M. K., Weiss, O., Kochig, S., Hirst, J. A., Oettgen, H. F.: Suppression and enhancement of the T cell-dependent production of antibody to SRBC in vitro by bacterial lipopolysaccharide. J. Immunol. 114, 738 (1975)

    PubMed  CAS  Google Scholar 

  36. Hoffmann, M. K., Galanos, C., Koenig, S., Oettgen, H. F.: B-cell activation by lipopolysaccharide. Distinct pathways for induction of mitosis and antibody production. J. Exp. Med. 146, 1640 (1977)

    Article  PubMed  CAS  Google Scholar 

  37. Izui, S., Lambert, P. H., Miescher, P. A.: In vitro demonstration of a particular affinity of glomerular basement membrane and collagen for DNA. A possible basis for a local formation of DNA-anti-DNA complexes in systemic lupus erythematosus. J. Exp. Med. 144, 428 (1976)

    Article  PubMed  CAS  Google Scholar 

  38. Izui, S., Lambert, P. H., Fournié, G., Türler, H., Miescher, P. A.: Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides. Identification of circulating DNA and renal localization of DNA-anti-DNA complexes. J. Exp. Med. 145, 1115 (1977)

    Article  PubMed  CAS  Google Scholar 

  39. Izui, S., Zaldivar, N. M., Scher, I., Lambert, P. H.: Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice. I. Anti-DNA induction by LPS without significant release of DNA in circulating blood. J. Immunol. 119, 2151 (1977)

    PubMed  CAS  Google Scholar 

  40. Izui, S., Kobayakawa, T., Louis, J., Lambert, P. H.: Induction of thymocytotoxic autoantibodies after injection of bacterial lipopolysaccharides in mice. Eur. J. Immunol. In press.

    Google Scholar 

  41. Jacobs, D. N., Morrison, D. C.: Stimulation of a T-independent primary anti-hapten response in vitro by TNP-lipopolysaccharide (TNP-LPS). J. Immunol. 114, 360 (1975)

    PubMed  CAS  Google Scholar 

  42. Johnson, A. G., Gaines, S., Landy, M.: Studies on the O antigen of Salmonella typhosa. V. Enhancement of antibody response to protein antigens by the purified lipopolysaccharide. J. Exp. Med. 103, 225 (1956)

    Article  PubMed  CAS  Google Scholar 

  43. Jones, J. M., Kind, P. D.: Enhancing effect of bacterial endotoxins on bone marrow cells in the immune response to SRBC. J. Immunol. 108, 1453 (1972)

    PubMed  CAS  Google Scholar 

  44. Koffler, D., Schur, P. H., Kunkel, H. G.: Immunological studies concerning the nephritis of systemic lupus erythematosus. J. Exp. Med. 126, 607 (1967)

    Article  PubMed  CAS  Google Scholar 

  45. Kolb, C., Di Pauli, R., Weiler, E.: Induction of IgG by Lipid A in the newborn mouse. J. Exp. Med. 139, 467 (1974)

    Article  PubMed  CAS  Google Scholar 

  46. Kunori, T., Ringden, O., Möller, E.: Optimal conditions for polyclonal antibody secretion and DNA synthesis in human blood and spleen lymphocytes by lipopolysaccharide. Scand. J. Immunol. 8, 451 (1978)

    Article  PubMed  CAS  Google Scholar 

  47. Lambert, P. H., Dixon, F. T.: Pathogenesis of the glomerulonephritis of NZB/W mice. J. Exp. Med. 127, 507 (1968)

    Article  PubMed  CAS  Google Scholar 

  48. Louis, J. A., Chiller, J. M., Weigle, W. O.: The ability of bacterial lipopolysaccharide to modulate the induction of unresponsiveness to a state of immunity. Cellular parameters. J. Exp. Med. 138, 1481 (1973)

    Article  PubMed  CAS  Google Scholar 

  49. Lüderitz, O., Westphal, O., Staub, A. M., Nikaido, H.: Isolation and chemical and immunological characterization of bacterial lipopolysaccharides. In: Microbial toxins. Weinbaum, G., Kadis, S., Ajl, S. J. eds., p. 145. Vol. 4. New York: Academic Press 1971

    Google Scholar 

  50. Melchers, F., Coutinho, A., Heinrich, G., Andersson, J.: Continuous growth of mitogen-reactive B lymphocytes. Scand. J. Immunol. 4, 353 (1975)

    Google Scholar 

  51. Miescher, P. A., Paronetto, F., Lambert, P. H.: Systemic lupus erythematosus. In: Textbook of immunopathology. Miescher, P. A., Müller-Eberhard, H. J. eds., 2nd edition pp. 963–101. New York: Grune and Stratton 1976

    Google Scholar 

  52. Miller, R. A., Gartner, S., Kaplan, A. S.: Stimulation of mitogenic responses in human peripheral blood lymphocytes by lipopolysaccharides: serum and T helper cell requirements. J. Immunol. 121, 2160 (1978)

    PubMed  CAS  Google Scholar 

  53. Möller, G., Andersson, J., Sjoberg, O.: Lipopolysaccharides can convert heterologous red cells into thymus-independent antigens. Cell. Immunol. 4, 416 (1972)

    Article  PubMed  Google Scholar 

  54. Ness, D. B., Smith, S., Telcott, J. A., Grumet, F. C.: T cell requirements for the expression of the lipopolysaccharide adjuvant effect in vivo: evidence for a T cell-dependent and a T cell-independent mode of action. Eur. J. Immunol. 6, 650 (1976)

    Article  PubMed  CAS  Google Scholar 

  55. Newburger, P. E., Kamueoka, T., Katz, D. H.: Potentiation of helper T cell function in IgE antibody responses by bacterial lipopolysaccharide (LPS). J. Immunol 113, 824 (1974)

    PubMed  CAS  Google Scholar 

  56. Nilsson, B. S., Sultzer, B. M., Bullock, W. W.: Purified protein derivative of tuberculin induces immunoglobulin production in normal mouse spleen cells. J. Exp. Med. 137, 127 (1973)

    Article  PubMed  CAS  Google Scholar 

  57. Nossal, G. J. V., Ada, G. L. In. Antigens, lymphoid cells and the immune response. Dixon, F. J., Kunkel, H. G. eds., New York: Academic Press 1971

    Google Scholar 

  58. Ornellas, E. P., Sanfilippo, F., Scott, D. W.: Cellular events in tolerance. IV. The effect of a graft-versus-host reaction and endotoxin on hapten- and carrier-specific tolerance. Eur. J. Immunol. 4, 587 (1974)

    Article  PubMed  CAS  Google Scholar 

  59. Parks, D. E., Doyle, M. V., Weigle, W. O.: Effect of lipopolysaccharide on immunogenicity and tolerogenicity of HGG in C57B1/6 nude mice: evidence for a possible B cell deficiency. J. Immunol. 119, 1923 (1977)

    PubMed  CAS  Google Scholar 

  60. Pearson, U.: Lipopolysaccharide-induced suppression of the primary immune response to a thymus-dependent antigen. J. Immunol. 118, 789 (1977)

    Google Scholar 

  61. Peavy, D., Adler, W., Smith, R.: The mitogenic effects of endotoxin and staphylococcal enterotoxin B on mouse spleen cells and human peripheral lymphocytes. J. Immunol. 105, 1453 (1970)

    PubMed  CAS  Google Scholar 

  62. Primi, D., Hammarström, L., Smith, C. I. E., Möller, G.: Characterization of self-reactive B cells by polyclonal B-cell activators. J. Exp. Med. 145, 21 (1977)

    Article  PubMed  CAS  Google Scholar 

  63. Ringden, O., Möller, E.: B cell mitogenic effects on human lymphocytes of rabbit anti-human B2-microglobulin. Scand. J. Immunol. 4, 171 (1975)

    Article  CAS  Google Scholar 

  64. Rubbech, J. A.: Molecular immunogenicity of bacterial lipopolysaccharide antigens: establishing a quantitative system. J. Immunol. 106, 993 (1971)

    Google Scholar 

  65. Schmitke, J. R., Dixon, F.: Immune response to a hapten coupled to an non-immunogenic carrier. Influence of lipopolysaccharide. J. Exp. Med. 136, 392 (1972)

    Article  Google Scholar 

  66. Scibienski, R. J., Gershwin, M. E.: Immunologic properties of protein-lipopolysaccharide complexes. I. Antibody response of normal, thymectomized and nude mice to a lysozyme-lipopolysaccharide complex. J. Immunol. 119, 504 (1977)

    PubMed  CAS  Google Scholar 

  67. Sjoberg, O., Andersson, J., Möller, G.: Lipopolysaccharides can substitute for helper cells in the antibody response in vitro. Eur. J. Immunol. 2, 326 (1972)

    Article  PubMed  CAS  Google Scholar 

  68. Skidmore, B. J., Chiller, J. M., Morrisson, D. C., Weigle, W. O.: Immunologic properties of bacterial lipopolysaccharide (LPS): Correlation between the mitogenic, adjuvant and immunogenic activities. J. Immunol. 117, 770 (1975)

    Google Scholar 

  69. Skidmore, B. J., Chiller, J. M., Morrison, D. C., Weigle, W. O.: Immunologic properties of bacterial lipopolysaccharides (LPS). Correlation between the mitogenic, adjuvant, and immunogenic activities. J. Immunol. 114, 770 (1975)

    PubMed  CAS  Google Scholar 

  70. Unanue, E. R.: The regulation of lymphocyte function by the macrophage. Immunol. Rev. 40, 227 (1978)

    Article  PubMed  CAS  Google Scholar 

  71. Uchiyama, T., Jacobs, D. M.: Modulation of immune response by bacterial lipopolysaccharide (LPS): Multifocal effects of LPS-induced suppression of the primary antibody response to a T-dependent antigen. J. Immunol. 121, 2340 (1978)

    PubMed  CAS  Google Scholar 

  72. Watson, J., Trankner, E., Cohn, M.: The use of bacterial lipopolysaccharides to show that two signals are required for the induction of antibody synthesis. J. Exp. Med. 138, 699 (1973)

    Article  PubMed  CAS  Google Scholar 

  73. Watson, J., Riblet, R.: Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic responses to lipopolysaccharide. J. Exp. Med. 140, 1147 (1974)

    Article  PubMed  CAS  Google Scholar 

  74. Yoshinaga, M., Yoshinaga, A., Waksman, B. H.: Regulation of lymphocyte responses in vitro. I. Regulatory effect of macrophages and thymus-dependent (T) cells on the response of thymus-independent (B) lymphocytes to endotoxin. J. Exp. Med. 136, 956 (1972)

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. WHO Immunology Research and Training Centre Lausanne/Genève, Institut de Biochimie, Université de Lausanne, Switzerland

    Jacques A. Louis & Paul-Henri Lambert

  2. Department of Medicine, University of Geneva, Switzerland

    Jacques A. Louis & Paul-Henri Lambert

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  1. Jacques A. Louis
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  2. Paul-Henri Lambert
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Editors and Affiliations

  1. Immunothérapie Expérimentale, Institut Pasteur, 28, rue du Docteur Roux, F-75016, Paris, France

    Louis Chedid

  2. Division d’Hématologie du Departement de Médecine, Hôpital Cantonal, 25, rue Micheli-du-Crest, CH-1211, Genève, Switzerland

    Peter A. Miescher

  3. Department of Molecular Immunology, Scripps Clinic and Research Foundation, 1066 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Hans J. Mueller-Eberhard

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© 1980 Springer-Verlag Berlin Heidelberg

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Louis, J.A., Lambert, PH. (1980). Lipopolysaccharides: From Immunostimulation to Autoimmunity. In: Chedid, L., Miescher, P.A., Mueller-Eberhard, H.J. (eds) Immunostimulation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-67809-7_5

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  • DOI: https://doi.org/10.1007/978-3-642-67809-7_5

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