The Physiology of Autoimmune Reactivities

  • M. A. R. Marcos
  • A. Sundblad
  • A. Grandien
  • F. Huetz
  • S. Avrameas
  • A. Coutinho


The three years frequency of the International Immunology Congresses make them appropriate to consider the place of progress in a given area. This decade was certainly marked by the structural solution of the T cell receptor problem, first announced in Kyoto (1983). However, if less dramatically, the common sense in other central areas of Immunology has also significantly evolved. This is particularly evident in what concerns autoimmunity. While in 1980 (Paris), there was hardly any mention of autoimmune reactivities in normal individuals, we are starting the 1989 Congress with Symposium lectures on the physiology of autoimmunity. The previous decade had seen the isolation and description of very promising animal models of spontaneous and induced autoimmune diseases, an increasingly powerful technology, and the demonstrations that “important” diseases (e.g., diabetes) were actually autoimmune. Many immunologists were attracted to this area, and the greatest expectations could be entertained. The present consensus is less optimistic and, in spite of much work, it seems that we have advanced very little towards the goal of treating and/or preventing autoimmune disease. We do feel, however, that the increasing attention given to autoreactivities in normal individuals, and the shift in perspective that this implies, have opened new possibilities: we can now compare physiology with pathology of autoreactivity, while not longer than 10 years ago, we were trying to understand autoimmune disease with no information, not even consideration, of what the physiology of those processes would be.


Normal Individual Natural Antibody Autoreactive Cell Natural Autoantibody Normal Immune System 
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  1. Andersson J, Coutinho A, Lernhardt W, Melchers F. (1977) Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte. Cell 10: 27–34PubMedCrossRefGoogle Scholar
  2. Avrameas S, Dighiero G, Lymberi P, Guilbert B (1983) Studies on natural antibodies and auto-anditodies. Ann. Immunol (Inst. Pasteur) 134D: 103Google Scholar
  3. Baccala R., Vo Quang T., Gilbert M, Ternynck T., Avrameas S. (1989) Two murine natural polyreactive autoantibodies are encoded by nonmutated germ-line genes. Proc Natl Acad Sci USA, 86: 4624.PubMedCentralPubMedCrossRefGoogle Scholar
  4. Cohn M, Langman R, Geckeier W (1980) Diversity 1980. In Progress in Immunology IV, Theme 3: Expression of Antigen receptors in lymphocytes and cellular activation mechanisms, M. Fougereau and J. Dausset Ed., Academic Press, pp. 153–202Google Scholar
  5. Coutinho A (1989) Beyond clonal selection and network. Immunol Rev 110, in pressGoogle Scholar
  6. Coutinho A, Forni L, Holmberg D, Ivars F, Vaz N, (1984) From an antigen- centered, clonal perspective of immune response to an organism centered, network perspective of autonomous activity in a self- referential immune system. Immunol Rev 79: 151–168PubMedCrossRefGoogle Scholar
  7. Coutinho A, Bandeira A, Pereira P, Portnoi D, Holmberg D, Martinez- A. C, Freitas A (1989) Selection of lymphocyte repertoires: the limits of clonal versus network organization. In: Symposia on Quantitative Biology, Vol. 54, Cold Spring Harbor Laboratory, N.Y., in press.Google Scholar
  8. Datta SK, Owen FL, Womack JE, Riblet RJ (1982) Analysis of recombinant imbred lines derived from “autoimmune” (NZB) and “high leukine” strains: independent multigenic systems control B cell hyperactivity, retrovirus expression and autoimmunity. J Immunol 129: 1539- 1544PubMedGoogle Scholar
  9. Dighiero G, Lymberi P, Mazie JC, Rouyre S, Butler-Browne GS, Whalen RG, Avrameas S (1983) Murine hybridomas secreting natural monoclonal antibodies reacting with self antigens. J Immunol 131: 2267–2272PubMedGoogle Scholar
  10. Dighiero G, Lymberi P, Holmberg D, Lundkvist I, Coutinho A, Avrameas S (1985) High frequency of natural autoantibodies in normal newborn mice. J Immunol 134: 765–771PubMedGoogle Scholar
  11. Gleichmann E, Gleichmann H and Wilke W (1976). Autoimmunization and lymphomagenesis in parent—Fl combinations differing at the major histocompatibility complex: model for spontaneous disease caused by altered self-antigens ? Transplant Rev 31: 156–224PubMedGoogle Scholar
  12. Goodnow CC, Crosbie J, Adelstein S, Lavoie TB, Smith-Gill SJ, Brink RA, Pritchard-Briscoe H, Wotherspoon JS, Lablay RH, Raphael K, Trent RJ, Basten A (1988) Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice. Nature 334: 676–682PubMedCrossRefGoogle Scholar
  13. Guilbert B, Dighiero G, Avrameas S, (1982) Naturally occuring antibodies against nine common antigens in human sera. I. Detection, isolation and characterisation. J Immunol 128: 2779–2787PubMedGoogle Scholar
  14. Herzenberg LA, Stall AM, Lalor PA, Sidman C, Moore WA, Parks DR, Herzenberg LA (1986) The Ly-1 B cell lineage. Immunol Rev 93: 81- 102PubMedCrossRefGoogle Scholar
  15. Holmberg D, Forsgren S, Ivars F, Coutinho A (1984) Reactions amongst IgM antibodies derived from normal, neonatal mice. Eur J Immunol, 14: 453–441CrossRefGoogle Scholar
  16. Hooijkaas H, Benner R, Pleasants JR, Wostmann BS (1984) Isotypes and specificities of immunoglobulin produced by germ-free mice fed chemically defined ultrafiltrered “antigen-free” diet. Eur J Immunol 14: 1127–1130PubMedCrossRefGoogle Scholar
  17. Huetz F, Jacquemart F, Pena Rossi C, Varela F Coutinho A (1988) Autoimmunity: the moving boundaries between physiology and pathology. J Autoimmunity 1: 507–518CrossRefGoogle Scholar
  18. Huetz F, Larsson-Sciard EL, Pereira P, Portnoi D, Coutinho A (1988) T cell dependence of “natural” auto-reactive B cell activation in the spleen of normal mice. Eur J Immunol 18: 1615–1622PubMedCrossRefGoogle Scholar
  19. Izui S, Kobayakawa R, Zrid MJ, Louis J, Lambert PH (1977) Mechanisms for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice. II. Correlation between anti-DNA antibodies induction and polyclonal antibody formation by various B-lymphocyte activators. J Immunol 119: 2157–2164PubMedGoogle Scholar
  20. Jerne NK (1974) Towards a network theory of the immune sustem. Ann Immunol (Inst. Pasteur) 125C: 373–389Google Scholar
  21. Klinman DM, Ishigatsubo Y, Steinberg AD (1988) Acquisition and maturation of expressed B cell repertoires in normal and autoimmune mice. J Immunol 141: 801–806PubMedGoogle Scholar
  22. Kotzin BL, Kappler JW, Marrack PC, Herron LR (1989) T cell tolerance to self antigens in New Zealand hybrid mice with lupus-like disease. J Immunol 143: 89–94PubMedGoogle Scholar
  23. Lo D, Burkly LC, Widera G, Cowing C, Flavell RA, Palmiter RD, Brinster RL (1988) Diabetes and tolerance in transgenic mice expressing Class II MHC molecule in pancreatic beta cells. Cell 53: 159–168PubMedCrossRefGoogle Scholar
  24. Marcos MAR, De La Hera A, Gaspar ML, Márquez C, Bellas C, Mampaso F, Toribio ML, Martinez-A, C (1986) Modification of emerging repertoires by immunosuppression in immunodeficient mice results in autoimmunity. Immunol Rev 94: 51–74Google Scholar
  25. Martinez -A C, Pereira P, Bernabé RR, Bandeira A, Larsson EL, Cazenave PA, Coutinho A (1984) Internal complementarities in the immune system: regulation of the expression of helper T-cell idiotypes. Proc Natl Acad Sci USA 81: 4520–4523PubMedCentralPubMedCrossRefGoogle Scholar
  26. Martinez -A C, Pereira P, Toribio ML, Marcos MAR, Bandeira A, De La Hera A, Márquez C, Cazenave PA, Coutinho A (1988) The participation of B cells and antibodies in the selection and maintenance of T cell repertoires. Immunol Rev 94: 51–74Google Scholar
  27. Naparstek J, Andra-Schwartz J, Mauser T, Wysock LJ, Bretiman L, Stollar B, Gefter M, Schwartz RS (1986) A single germ-line Vh gene segment of normal A/J mice encodes auto-antibodies characteristic of systemic lupur erythematosus. J Exp Med 164: 614–626PubMedCrossRefGoogle Scholar
  28. Nemazee DA, Burki D (1989) Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC Class I antibody gene. Nature 337: 562–566PubMedCrossRefGoogle Scholar
  29. Nossal GJV, Pike BL (1980) Antibody receptor diversity and diversity of signals. In Progress in Immunology IV, Theme 3: Expression of Antigen receptors in lymphocytes and cellular activation mechanisms, M. Fougereau and J. Dausset Ed., Academic Press, pp. 136–153Google Scholar
  30. Pereira P, Larsson EL, Forni L, Bandeira A, Coutinho A (1985) Natural effector T lymphocytes in normal mice. Proc Natl Acad Sci USA 82: 7691–7695PubMedCentralPubMedCrossRefGoogle Scholar
  31. Pereira P, Forni L, Larsson EL, Cooper M, Heusser C, Coutinho A (1986) Autonomous activation of B and T cells in antigen-free mice. Eur J Immunol 16: 685–688PubMedCrossRefGoogle Scholar
  32. Pobor G, Pettersson S, Larsson EL, Coutinho A (1982) Development of a quantitative assay detecting all T cells mediating helper effects for B lymphocytes, regardless of their specificity. Scand J Immunol, 15: 134 (Abst.)Google Scholar
  33. Portnoi D, Freitas A, Holmberg D, Bandeira A, Coutinho A (1986) Immunocompetent autoreactive B lymphocytes are activated cycling cells in normal mice. J Exp Med 164: 25–35PubMedCrossRefGoogle Scholar
  34. Prabhakar BS, Saegusa J, Onodera R, Notkins AL (1984) Lymphocytes capable of making monoclonal autoantibodies that react with multiple organs are a common feature of the normal B cell repertoire. J Immunol 133: 2815–2817PubMedGoogle Scholar
  35. Schlomchik MJ, Marshak-Rochstein CB, Wolfowicz TL, Rothstein A, Weigert MG (1987) The role of clonal selection and somatic mutation in autoimmunity. Nature 328: 805–811CrossRefGoogle Scholar
  36. Stewart J, Varela FJ, Coutinho A (1989) The relationship between connectivity and tolerance as revealed by computer stimulation of the immune network: some lessons for an understanding of autoimmunity. J Autoimmunity 2: 15–23CrossRefGoogle Scholar
  37. Theofilopoulos AN, Dixon FJ (1985) Murine models of systemic lupus erythematosus. Adv Immunol 37: 269–390PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • M. A. R. Marcos
  • A. Sundblad
  • A. Grandien
  • F. Huetz
  • S. Avrameas
  • A. Coutinho

There are no affiliations available

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