Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B

Hiroshi Watanabe, Gérard Garnier, Antonella Circolo, Rick A. Wetsel, Phil Ruiz, V. Michael Holers, Susan A. Boackle, Harvey R. Colten, Gary S. Gilkeson

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153 Scopus citations

Abstract

In systemic lupus erythematosus, the renal deposition of complement- containing immune complexes initiates an inflammatory cascade resulting in glomerulonephritis. Activation of the classical complement pathway with deposition of C3 is pathogenic in lupus nephritis. Although the alternative complement pathway is activated in lupus nephritis, its role in disease pathogenesis is unknown. To determine the role of the alternative pathway in lupus nephritis, complement factor B-deficient mice were back-crossed to MRL/lpr mice. MRL/lpr mice develop a spontaneous lupus-like disease characterized by immune complex glomerulonephritis. We derived complement factor B wild-type (B(+/+)), homozygous knockout (B(-/-)), and heterozygous (B(+/-)) MRL/lpr mice. Compared with B(+/-) or B(+/+) mice, MRL/lpr B(-/-) mice developed significantly less proteinuria, less glomerular IgG deposition, and decreased renal scores as well as lower IgG3 cryoglobulin production and vasculitis. Serum C3 levels were normal in the B(-/-)-mice compared with significantly decreased levels in the other two groups. These results suggest that: 1) factor B plays an important role in the pathogenesis of glomerulonephritis and vasculitis in MRL/lpr mice; and 2) activation of the alternative pathway, either by the amplification loop or by IgA immune complexes, has a prominent effect on serum C3 levels in this lupus model.

Original languageEnglish (US)
Pages (from-to)786-794
Number of pages9
JournalJournal of Immunology
Volume164
Issue number2
DOIs
StatePublished - Jan 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Watanabe, H., Garnier, G., Circolo, A., Wetsel, R. A., Ruiz, P., Holers, V. M., Boackle, S. A., Colten, H. R., & Gilkeson, G. S. (2000). Modulation of renal disease in MRL/lpr mice genetically deficient in the alternative complement pathway factor B. Journal of Immunology, 164(2), 786-794. https://doi.org/10.4049/jimmunol.164.2.786