IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice.

Abstract

(NZB x NZW)F1 female (BW) mice spontaneously develop an autoimmune disease, characterized by the production of autoantibodies (autoAbs) and glomerulonephritis, which can be delayed by neutralizing IFN-gamma Abs and accelerated by IFN-gamma injections. To define the role of IFN-gamma in the pathogenesis of glomerulonephritis, we established a population of BW mice deficient in IFN-gammaR (BWgammaR[-/-]) by repeated crossing; these mice were compared with BWgammaR(+/+) and +/- littermates. Of the BWgammaR(+/+) and +/- mice, 50% showed immune complex glomerulonephritis with heavy proteinuria at 8 mo of age, while only 10% of the BWgammaR(-/-) mice were affected at 14 mo. The serum concentration of anti-dsDNA and anti-histone Abs was dramatically reduced in BWgammaR(-/-) mice. The role of IFN-gamma in promoting class switch to IgG2a and IgG3 could not fully account for the impaired production of anti-dsDNA in BWgammaR(-/-) animals since, IgM and IgG1 levels were also reduced. There was a high incidence of B cell lymphoma in the BWgammaR(-/-) mice, which might be related to the suppression of autoAb production. Thus, the absence of glomerulonephritis in BWgammaR(-/-) mice is likely due to a dramatic yet unexplained effect of the inactivation of IFN-gamma signaling on autoAb production.

• Authors: C Haas, B Ryffel, M Le Hir
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 160 Issue 8 Pg. 3713-8 (Apr 15 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9558072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Antinuclear
• Autoantibodies
• DNA Primers
• Immunoglobulin G
• Receptors, Interferon
• interferon gamma receptor
• Interleukin-4
• Interferon-gamma

Topics

• Animals
• Antibodies, Antinuclear (biosynthesis)
• Autoantibodies (biosynthesis)
• Base Sequence
• DNA Primers (genetics)
• Disease Models, Animal
• Female
• Immunoglobulin G (blood)
• In Vitro Techniques
• Interferon-gamma (biosynthesis)
• Interleukin-4 (biosynthesis)
• Lupus Nephritis (etiology, pathology, prevention & control)
• Lymphoma (etiology, pathology)
• Male
• Mice
• Mice, Inbred NZB
• Mice, Knockout
• Polymerase Chain Reaction
• Receptors, Interferon (genetics, immunology)
• T-Lymphocytes (immunology)