Skip to main content
SpringerLink
Log in

The NZB × SWR Model: Insights into Viral, Immunologic, and Genetic Factors

  • Chapter
Systemic Lupus Erythematosus

  • 92 Accesses

Abstract

The primary etiologic mechanism of systemic lupus erythematosus (SLE) is unknown. SLE in humans is probably not a single entity, but a heterogeneous group of diseases with similar clinical and immunopathologic features [1]. A genetic predisposition clearly plays a role in the development of SLE, but the genetic interactions that occur in this disorder are multiple and complex, and very little is known about the mechanism of action of such genetic factors [2]. Furthermore, the etiologic role of viruses in human SLE is disputable; retroviruses have been implicated by some investigators [3–6], whereas other have not been able to reproduce such findings [7, 8]. Discrepancies are also prevalent among the vast number of studies on the immune system in SLE [1]. It is not clear whether the immunologic abnormities are the cause of the disease or its consequence. Because of this complexity, several animal models are being investigated to define the fundamentalal mechanism of the disease.

The studies described in this paper were supported by National Institutes of Health grant no. RO1 CA 31789.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Tsokos GC, Balow JE (1984) Cellular immune responses in systemic lupus erythematosus. Prog Allergy 35: 93–161

    CAS  PubMed  Google Scholar 

  2. Arnett FC, Reveille JD, Wilson RW, Provost TT, Bias WB (1984) Systemic lupus erythematosus: current state of the genetic hypothesis. Semin Arthritis Rheum 14: 24–35

    Article  CAS  PubMed  Google Scholar 

  3. Mellors RC, Mellors JW (1976) Antigen related to mammalian type-C RNA viral p30 proteins is located in renal glomeruli in human systemic lupus erythematosus. Proc Natl Acad Sci USA 73: 233–237

    Article  CAS  PubMed  Google Scholar 

  4. Lewis RM, Tanneberg W, Smith C, Schwartz RS (1974) C-type viruses in systemic lupus erythematosus. Nature 252: 78–79

    Article  CAS  PubMed  Google Scholar 

  5. Strand M, August JT (1974) Type-C RNA virus gene expression in human tissue. J. Virol 14: 1584–1596

    CAS  PubMed  Google Scholar 

  6. Panem S, Ordonez NG, Kirstein WH, Katz AI, Spargi BH (1976) C-type virus espression in systemic lupus erythematosus. N Engl J Med 295: 470–475

    Article  CAS  PubMed  Google Scholar 

  7. Philips PE (1978) Type C onco RNA virus studies in systemic lupus erythematosus. Arthritis Rheum 21 [Suppl 5]: S 76–81

    Article  Google Scholar 

  8. Kimura M, Andoh T, Kai K (1980) Failure to detect type-C virus p30-related antigen in systemic lupus erythematosus: false-positive reaction due to protease activity. Arthritis Rheum 23: 111–113

    Article  CAS  PubMed  Google Scholar 

  9. Howie JB, Helyer BJ (1968) The immunology and pathology of NZB mice. Adv Immunol 9: 215–268

    Article  CAS  PubMed  Google Scholar 

  10. Murphy ED, Roths JB (1978) Autoimmunity and lymphoproliferation: induction by mutant gene 1pr, and acceleration by a male-associated factor in strain B x SB mice. In: Rose NE, Bigazzi PE, Warner NL (eds) Genetic control of autoimmune disease. Elsevier/North Holland, Amsterdam, pp 207–221

    Google Scholar 

  11. Prud’homme GJ, Fieser TM, Dixon FJ, Theofilopoulos AN (1984) B cell-tropic interleukins in murine systemic lupus erythematosus. Immunol Rev 78: 160–183

    Google Scholar 

  12. Izui S, Kelley VE, Kazushige M, Yoshida H, Roths JB, Murphy ED (1984) Induction of various autoantibodies by mutant gene Ipr in several strains of mice. J Immunol 133: 227–233

    CAS  PubMed  Google Scholar 

  13. Hang L, Aguado MT, Dixon FJ, Theofilopoulos AN (1985) Indiction of severe autoimmune disease in normal mice by simultaneous action of multiple immunostimulators. J Exp Med 161: 423–428

    Article  CAS  PubMed  Google Scholar 

  14. Pisetsky DS, Caster SA, Roths JB, Murphy ED (1982) Gene control of the anti-DNA antibody response. J Immunol 128: 2322–2325

    CAS  PubMed  Google Scholar 

  15. Giroir BP, Raps EC, Lewis RM, Borel Y (1983) Nucleoside-specific suppression in MRL/ MP +/+ mice. Cell Immunol 75: 337–347

    Article  CAS  PubMed  Google Scholar 

  16. Datta SK, Manny N, Andrzejewski C, Andre-Schwartz J, Schwartz RS (1978) Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand Black mice. I. Xenotropic virus. J Exp Med 147: 854–871

    Article  CAS  PubMed  Google Scholar 

  17. Eastcott JW, Schwartz RS, Datta SK (1983) Genetic analysis of the inheritence of B cell hyperactivity in relation to the development if autoantibodies and glomerulonephritis in NZB × SWR crosses. J Immunol 131: 2232–2239

    CAS  PubMed  Google Scholar 

  18. Kelley VE, Winkelstein A (1980) Age-and sex-related glomerulonephritis in New Zealand White mice. Clin Immunol Immunopathol 16: 142–150

    Article  CAS  PubMed  Google Scholar 

  19. Yoshiki T, Mellors RC, Strand M, August JT (1974) The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune-complex glomerulonephritis of New Zealand mice. J Exp Med 140: 1011–1027

    Article  CAS  PubMed  Google Scholar 

  20. Datta SK, McConahey PJ, Manny N, Theofilopoulos AN, Dixon FJ, Schwartz RS (1978) Genetic studies of autoimmunity and retrovirus expression in New Zealand Black mice. II. The viral envelope glycoprotein gp70. J Exp Med 147: 872–881

    Article  CAS  PubMed  Google Scholar 

  21. Weiss R, Teich N, Varmus H, Coffin J (eds) (1982) RNA tumor viruses. Molecular biology of tumor viruses. Cold Spring Harbor, Laboratories, New York (Cold Spring Harbor Laboratories monograph no. IOC)

    Google Scholar 

  22. Levy JA, Kazan P, Varnier O, Kleinman H (1975) Murine xenotropic type-C virus. I. Distribution and further characterization of the virus in NZB mice. J Virol 16: 844–853

    CAS  PubMed  Google Scholar 

  23. Levy JA (1976) Endogenous C-type viruses: double agents in natural life processes. Biomedicine 24: 84–93

    CAS  PubMed  Google Scholar 

  24. East J (1970) Immunopathology and neoplasms in NZB and SJL/J mice. Prog. Exp Tumor Res 13: 84–134

    CAS  PubMed  Google Scholar 

  25. Datta SK, Schwartz RS (1976) Genetics of expression of xenotropic virus and autoimmunity in NZB mice. Nature 263: 412–415

    Article  CAS  PubMed  Google Scholar 

  26. Datta SK, Schwartz RS (1977) Mendelian segregation of loci controlling xenotropic virus production in NZB crosses. Virology 83: 449–452

    Article  CAS  PubMed  Google Scholar 

  27. Datta SK, Owen FL, Womak JE, Riblet RJ (1982) Analysis of recombinant inbred line derived from autoimmune (NZB) and high-leukemia (C58) strains: independent multigenic systems control B cell hyperactivity, retrovirus expression and autoimmunity. J Immunol 129: 1539–1544

    CAS  PubMed  Google Scholar 

  28. Izui S, McConahey PJ, Clark JP, Hang LM, Hara I, Dixon FJ (1981) Retroviral gp70 immune complexes in NZB x NZW F2 mice with murine lupus nephritis. J Exp Med 154: 517–528

    Article  CAS  PubMed  Google Scholar 

  29. Maruyama N, Furukawa F, Nakai Y, Yutaka S, Ohta K, Ozaki S, Hirose S, Shirai T (1983) Genetic studies of autoimmunity in New Zealand mice. IV. Contribution of NZB and NZW genes to the spontaneous occurrence of retroviral gp70 immune complexes in ( NZB x NZW) F, hybrid and correlation to renal disease. J Immunol 130: 740–746

    CAS  PubMed  Google Scholar 

  30. Barthold DR, Kysela SJ, Steinberg AD (1974) Decline in suppressor T cell function with age in female NZB mice. J Immunol 112: 9–16

    CAS  PubMed  Google Scholar 

  31. Cantor H, McVay-Boudreau L, Hugenberger J, Naidorf K, Shen FW, Gershon RK (1978) Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. J Exp Med 147: 1116–1125

    Article  CAS  PubMed  Google Scholar 

  32. Shirai T, Hayakawa K, Okumura KO, Tada T (1978) Differential cytotoxic effect of natural thymocytotoxic autoantibody of NZB mice on functional subsets of T cell. J Immunol 120: 1924–1929

    CAS  PubMed  Google Scholar 

  33. Raveche ES, Steinberg AD, Klassen LW, Tjio JH (1978) Genetic studies in NZB mice. I. Spontaneous autoantibody production. J Exp Med 147: 1487–1501

    Article  CAS  PubMed  Google Scholar 

  34. Primi D, Hammarstrom L, Smith CIE (1978) Genetic control of lymphocyte suppression. I. Lack of suppression in aged NZB mice is due to a B cell defect. J Immunol 121: 2241–2243

    CAS  PubMed  Google Scholar 

  35. Manny N, Datta SK, Schwartz RS (1979) Synthesis of IgM by cells of NZB and SWR mice and their crosses. J Immunol 122: 1220–1227

    CAS  PubMed  Google Scholar 

  36. Taurog JD, Raveche ES, Smathers PA, Glimcher LH, Huston DP, Hansen CT, Steinberg AD (1981) T cell abnormalities in NZB mice occur independently of autoantibody production. J Exp Med 153: 221–234

    Article  CAS  PubMed  Google Scholar 

  37. Gershwin ME, Castels JJ, Ikeda RM, Erickson K, Montero J (1979) Studies of congenitally immunologic mutant New Zealand mice. I. Autoimmune features of hereditary asplenic ( Dh/ +) NZB mice, reduction of naturally occurring thymocytotoxic antibody and normal suppressor function. J Immunol 122: 710–717

    CAS  PubMed  Google Scholar 

  38. Moutsopolos HM, Boehm-Truitt M, Kassan SS, Chused TM (1977) Demonstration of activation of B-lymphocytes in New Zealand Black mice at birth by an immunoradiometric assay for murine IgM. J Immunol 119: 1639–1644

    Google Scholar 

  39. Manohor V, Brown E, Leiserson WM, Chused TM (1982) Expression of Lyt-1 by a subset of B lymphocytes. J Immunol 129: 532–538

    Google Scholar 

  40. Hayakawa K, Hardy RR, Parks DR, Herzenberg LA (1983) The “Ly-1 B” cell subpopulation in normal, immunodefective and autoimmune mice. J Exp Med 157: 202–218

    Article  CAS  PubMed  Google Scholar 

  41. Nakajima PB, Datta SK, Schwartz RS, Huber BT (1979) Localization of spontaneously hyperactive B cells of NZB mice to a specific B subset. Proc Natl Acad Sci USA 76: 4613–4616

    Article  CAS  PubMed  Google Scholar 

  42. Taurog JD, Montsopoulos HM, Rosenberg YJ, Chused TM, Steinberg AD (1979) CBA/N X-linked B cell defect prevents NZB B-cell hyperactivity in F1 mice. J Exp Med 150: 31–43

    Article  CAS  PubMed  Google Scholar 

  43. Hayakawa K, Hardy RR, Honda M, Herzenberg LA, Steinberg AD, Herzenberg LA (1984) Ly-I B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. Proc Natl Acad Sci USA 81: 2494–2498

    Article  CAS  PubMed  Google Scholar 

  44. Ebling F, Hahn BH (1980) Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus: comparison of antibodies in serum and renal eluates. Arthritis Rheum 23: 392–403

    Article  CAS  PubMed  Google Scholar 

  45. Rothfield NF, Stollar BD (1967) The relation of immunoglobulin class, pattern of antinuclear antibody and complement-fixing antibodies to DNA in sera of patients with systemic lupus erythematosus. J Clin Invest 46: 1784–1794

    Article  Google Scholar 

  46. Talal N (1976) Disordered immunologic regulation and autoimmunity. Transplant Rev 31: 240–263

    CAS  PubMed  Google Scholar 

  47. Raveche ES, Novotny EA, Hansen CT, Tjio JH, Steinberg AD (1981) Genetic studies in NZB mice. V. Recombinant inbred lines demonstrate that separate genes control autoimmune phenotype. J Exp Med 153: 1187–1197

    Article  CAS  PubMed  Google Scholar 

  48. Pisetsky DS, McCarty GA, Peters DV (1980) Mechanisms of autoantibody production in autoimmune MRL mice. J Exp Med 152: 1302–1310

    Article  CAS  PubMed  Google Scholar 

  49. Jerne NK (1974) Towards a network theory of the immune system. Ann Immunol (Paris) 125: 373–389

    CAS  Google Scholar 

  50. Bona CA (1981) Idiotypes and lymphocytes. Academic, New York

    Google Scholar 

  51. Wigzell H, Binz H, Frischknecht H, Peterson P, Sege K (1978) Possoble roles of auto-antiidiotypic immunity in autoimmune disease In: Rose NE, Bigazzi PE, Warner NL (eds) Genetic control of autoimmune disease. Elsevier/North Holland, Amsterdam, pp 327–342

    Google Scholar 

  52. Abdou NI, Wall H, Lindsley HB, Halsey JF, Suzuki T (1981) Network theory in autoimmunity. In vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus. J Clin Invest 67: 1297–1304

    Article  CAS  PubMed  Google Scholar 

  53. Wasserman NH, Penn AS, Freimuth PI, Treptow N, Wentzerl S, Cleveland WL, Erlanger BF (1982) Anti-idiotype route to antiacetylcholine receptor antibodies in experimental myasthenia gravis. Proc Natl Acad Sci USA 79: 4810–4814

    Article  Google Scholar 

  54. Hahn BH, Ebling FM (1983) Suppression of NZB/NZW murine mephritis by administration of a syngeneic monoclonal antibody to DNA. Possible role of anti-idiotypic antibodies. J Clin Invest 71: 1728–1736.

    Article  CAS  PubMed  Google Scholar 

  55. Titelbaum D, Rauch J, Stoller BD, Schwartz RS (1984) In vivo effects of antibodies against a high frequency idiotype of anti-DNA antibodies in MRL mice. J Immunol 132: 1282–1285

    Google Scholar 

  56. Datta SK, Sollar BD, Schwartz RS (1983) Normal mice espress idiotypes related to autoantibody idiotypes of lupus mice. Proc Natl Acad Sci USA 80: 2723–2727

    Article  CAS  PubMed  Google Scholar 

  57. Datta SK (1984) Anti-DNA antibody idiotypes in normal and lupus mice. In: Sercarz E, Cantor H, Chess L (eds) Regulation of the immune system, UCLA Symposia on molecular and cellular biology, vol 18. Liss. New York, pp 877–886

    Google Scholar 

  58. Schwartz RS, Stoller BD (1985) Origins of anti-DNA autoantibodies. J Clin Invest 75: 321–327

    Article  CAS  PubMed  Google Scholar 

  59. Gavalchin J, Nicklas JA, Eastcott JW, Madaio MP, Stoller BD, Schwartz RS, Datta SK (1985) Lupus-prone (SWR × NZB) F1 mice produce potentially nephritogenic autoantibodies inherited from the normal SWR parent. J Immunol 134: 885–894

    CAS  PubMed  Google Scholar 

  60. Koffler D, Carr R, Agnello V, Thoburn R, Kunkel HG (1971) Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease. J Exp Med 134: 294–312

    Article  CAS  PubMed  Google Scholar 

  61. Rubin RL, Carr RI (1972) Anti-DNA activity of IgG F (ab’)2 from normal human serum. J Immunol 122: 1604–1607

    Google Scholar 

  62. Fish F, Ziff M (1982) The in vitro and in vivo induction of anti-double-strandes DNA antibodies in normals and autoimmune mice. J Immunol 128: 409–414

    CAS  PubMed  Google Scholar 

  63. Kobayakawa T, Louis J, Izui S, Lambert PH (1979) Autoimmune responses to DNA, red blood cells and thymocyte antigens in association with polyclonal antibody synthesis during experimental African trypanisomiasis. J Immunol 122: 296–301

    CAS  PubMed  Google Scholar 

  64. Datta SK, Naparstek Y, Schwartz RS (1986) In vitro production of an anti-DNA indiotype by lymphocytes of normal subjects and patients with systemic lupus erythematosus Clin Immunol Immunopathol 38: 302–318

    CAS  Google Scholar 

  65. Paul WE, Bona CA (1982) Regulatory idiotopes and immune networks: a hypothesis. Immunol Today 3: 230–234

    Article  CAS  Google Scholar 

  66. Hornbeck PV, Lewis GK (1983) Idiotype connectance in the immune system. I. Expression of a cross-reactive idiotype on induced anti-p-azophenylarsonate antibodies and on endogenous antibodies not specific for arsonate. J Exp Med 157: 1116–1136

    Article  CAS  PubMed  Google Scholar 

  67. Lawrence Y, Agodoa C, Gauthier VJ, Mannik M (1985) Antibody localization in the glomerular basement membrane may precede in situ immune deposit formation in rat glomeruli. J Immunol 134: 880–884

    Google Scholar 

  68. Barnes JL, Venkatachalam MA (1984) Enhancement of glomerular immune complex deposition by a circulating polycation. J Exp Med 160: 286–293

    Article  CAS  PubMed  Google Scholar 

  69. Datta SK, Schwartz RS (1978) Genetic, viral and immunologic aspects of autoimmune disease in NZB mice. In: Rose NR, Bigazzi PE, Warner NL (eds) Genetic control of autoimmune disease. Elsevier/North Holland, Amsterdam, pp 193–206

    Google Scholar 

  70. Haspel MV, Onodera T, Prabhakar BS, McClintock PR, Essani K, Roy UR, Yagihashi S, Notkins AL (1983) Multiple organ-reactive monoclonal autoantibodies. Nature 304: 73–76

    Article  CAS  PubMed  Google Scholar 

  71. Sakaguchi S, Fukuma K, Kuribayashi K, Mesuda T (1985) Organ specific autoimmune diseases induced in mice by elimination of T cell subset. J Exp Med 161: 72–87

    Article  CAS  PubMed  Google Scholar 

  72. Knight JG, Adams DD (1978) Three genes for lupus nephritis in NZB x NZW mice. J Exp Med 147: 1653–1660

    Article  CAS  PubMed  Google Scholar 

  73. Hirose S, Nagasawa R, Sakikawa I, Hamaoki M, Ishida Y, Sato H, Shirai T (1983) Enhancing effect of H-2 linked NZW gene(s) on the autoimmune traits of ( NZB x NZW) F, mice. J Exp Med 158: 228–233

    Article  CAS  PubMed  Google Scholar 

Download references

Authors
  1. S. K. Datta
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Datta, S.K. (1987). The NZB × SWR Model: Insights into Viral, Immunologic, and Genetic Factors. In: Systemic Lupus Erythematosus. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71642-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71642-3_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71644-7

  • Online ISBN: 978-3-642-71642-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation