Elsevier

Advances in Immunology

Volume 37, 1985, Pages 269-390
Advances in Immunology

Murine Models of Systemic Lupus Erythematosus1

https://doi.org/10.1016/S0065-2776(08)60342-9Get rights and content

Publisher Summary

This chapter reviews the histopathologic, serologic, lymphocytic, virological, hormonal, and genetic characteristics of murine models of systemic lupus erythematosus (SLE). The pathogenetic mechanisms underlying murine SLE are highly complex, apparently well-programmed genetically, but still diverse and their bases not as yet well defined. Significant serologic and cellular experimental data support the statement that the final immunopathologic perturbation in murine (and human) SLE is a B lymphocyte hyperactivity with corresponding enhancement of serum antibodies and autoantibodies, particularly IgG, and consequent formation of pathogenic antigen–antibody ICs. On the basis of the available data, it appears that this B cell hyperactivity is polyclonal but not necessarily panclonal in nature, because not only antibodies against a wide array of autoantigens but also antibodies against incidental antigens, such as haptens, can be detected. The presence of autoantibodies and of their idiotypes in some recombinant lupus x normal murine lines expressing the normal partner's V genes, normal mice in which an exogenous or endogenous (Ipr gene) immunostimulator has been introduced, and unmanipulated normal mice indicate that lupus mice are not unique in their structural genetic Ig elements, whose presence determines the development of their autoimmune disease. The cause of B cell hyperactivity in lupus has not yet been fully elucidated. Autonomous B cell maturation does not appear likely, because B cell proliferation and differentiation in lupus mice was found to be dependent on the same number of accessory signals as in normal mice.

References (608)

  • E.N. Tan

    Immunopathology and pathogenesis of cutaneous involvement in systemic lupus erythematosus

    J. Invest. Dermatol.

    (1976)
  • M. Bielschowsky et al.

    Spontaneous anemia in mice of the NZB/B1 strain

    Proc. Unit. Otago Med. School

    (1959)
  • B.J. Helyer et al.

    Renal disease associated with positive lupus erythematosus in cross-bred strains of mice

    Nature (London)

    (1963)
  • E.D. Murphy et al.

    Autoimmunity and lymphoproliferation: Induction by mutant gene lpr and acceleration by a male-associated factor in strain BXSB mice

  • E.D. Murphy

    Lymphoproliferation (Ipr) and other single-locus models for murine lupus

  • B.S. Andrews et al.

    Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains

    J. Exp. Med.

    (1978)
  • S.E. Walker et al.

    Palmerston North mice, a new animal model of systemic lupus erythematosus

    J. Lab. Clin. Med.

    (1978)
  • W.F. Davidson

    Immunologic abnormalities of the autoimmune mouse, Palmerston North

    J. Immunol.

    (1982)
  • M.C. Green et al.

    Motheaten, an immunodeficient mutant of the mouse. I. Genetics and pathology

    J. tiered.

    (1975)
  • L.D. Schultz et al.

    Motheaten, an immunodeficient mutant of the mouse. II. Depressed immune competence and elevated serum immunoglobulins

    J. Immunol.

    (1976)
  • W.F. Davidson et al.

    Phenotypic and functional effects of the motheaten gene on murine B and T lymphocytes

    J. Immunol.

    (1979)
  • K. Fischer-Lindahl et al.

    Maternally transmitted target antigen for unrestricted killing by NZB T lymphocytes

    J. Exp. Med.

    (1980)
  • K. Fischer-Lindahl et al.

    Mta, a maternally inherited cell surface antigen of the mouse, is transmitted in the egg

    Proc. Natl. Acad. Sci. U.S.A.

    (1982)
  • M.M. Huston et al.

    Differences in maternal lineages of New Zealand Black mice defined by restriction endonuclease analysis of mitochondrial DNA and by expression of maternally transmitted antigen

    J. Exp. Med.

    (1983)
  • R. Smith et al.

    Primary cell-mediated lympholysis response to a maternally transmitted antigen

    J. Exp. Med.

    (1982)
  • M. Bielschowsky et al.

    Origin of inbred NZ mouse strains

    Cancer Res.

    (1970)
  • Callahan, G., Dixon, F. J., and Theofilopoulos, A. N. (1984). Ia antigens of AKR and C3H mice are not identical, and...
  • P.S. Cronin et al.

    J. Immunol.

    (1984)
  • J.B. Roths et al.

    Modification of expression of Ipr by background genome

    Fed. Proc, Fed. Am. Soc. Exp. Biol.

    (1983)
  • J.B. Roths et al.

    A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice

    J. Exp. Med.

    (1984)
  • A.N. Theofilopoulos et al.

    Etiopathogenesis of murine SLE

    Immunol. Rev.

    (1981)
  • N.L. Warner

    Genetic aspects of autoimmune disease in animals

  • P.H. Lambert et al.

    Pathogenesis of the glomerulonephritis of NZB/W mice

    J. Exp. Med.

    (1968)
  • T. Yoshiki et al.

    The viral envelope glycoprotein of murine leukemia virus and the pathogenesis of immune complex glomerulonephritis of New Zealand mice

    J. Exp. Med.

    (1974)
  • J.H. Slack et al.

    Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice

    J. Immunol.

    (1984)
  • F.J. Dixon et al.

    Pathogenesis of immune complex glomerulonephritis of New Zealand mice

    J. Exp. Med.

    (1971)
  • F. Ebling et al.

    Restricted subpopulations of DNA antibodies in kidneys of mice with systemic lupus

    Arthritis Rheum.

    (1980)
  • T. Caulin-Glaser et al.

    Nondissociating cationic immune complexes can deposit in glomerular basement membrane

    J. Exp. Med.

    (1983)
  • G.R. Gallo et al.

    Charge of circulating immune complexes as a factor in glomerular basement membrane localization in mice

    J. Clin. Invest.

    (1981)
  • T. Oite et al.

    Quantitative studies of in situ immune complex glomerulonephritis in the rat induced by planted, cationized antigen

    J. Exp. Med.

    (1982)
  • V.J. Gauthier et al.

    Effect of cationized antibodies in preformed immune complexes on deposition and persistance in renal glomeruli

    J. Exp. Med.

    (1982)
  • M.E. Gershwin et al.

    Age-dependent loss in New Zealand mice of morphological and functional characteristics of thymic epithelial cells

    J. Immunol.

    (1978)
  • J.F. Bach et al.

    Studies on thymus products. Presence of serum “thymic activity” in adult NZB and (NZBxNZW)F1 mice

    Clin. Exp. Immunol.

    (1973)
  • M.E. Gershwin et al.

    Study of thymic factors. II. Failure of thymosin to alter the natural history of NZB and NZB/NZW mice

    Arthritis Rheum.

    (1976)
  • J. Mehta et al.

    Effect of altered lymphocyte function on immunologic disorders in NZB/NZW mice: III. Acceleration of disease by thymosin

    Arthritis Rheum.

    (1978)
  • L. Accinni et al.

    Degenerative vascular disease and myocardial infarction in mice with lupus-like syndrome

    Am. J. Pathol.

    (1979)
  • L.M. Hang et al.

    (NZB x BXSB)F1 hybrid: A model of acute lupus and coronary vascular disease with myocardial infarction

    J. Exp. Med.

    (1981)
  • L.M. Hang et al.

    The role of hypertension in coronary vascular disease and myocardial infarcts associated with SLE

    Arthritis Rheum.

    (1983)
  • J.H.M. Berden et al.

    Analysis of vascular lesions in murine SLE

    J. Immunol.

    (1983)
  • A.M. Denman et al.

    Proliferative activity in the lymphatic tissues of germ-free New Zealand Black mice

    Int. J. Cancer

    (1970)
  • Cited by (1466)

    View all citing articles on Scopus
    1

    This is Publication No. 3665IMM from the Department of Immunology, Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California 92037. Our work cited herein was supported, in part, by National Institutes of Health Grants AI-07007, AM-31023, AM-33826, National Cancer Institute Grants CA-27489 and AG-01743 and the Cecil H. and Ida M. Green Endowment Fund

    View full text