Fcγ receptor IIB-deficient mice develop goodpasture's syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease

Akira Nakamura, Takae Yuasa, Azusa Ujike, Masao Ono, Toshihiro Nukiwa, Jeffrey V. Ravetch, Toshiyuki Takai

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

The combination of hemorrhagic pneumonitis and rapidly progressive glomerulonephritis is a characteristic feature of Goodpasture's syndrome (GPS), an autoimmune disease resulting from the interaction of pathogenic anti-collagen type IV (C-IV) antibodies with alveolar and glomerular basement membranes. Lack of a suitable animal model for this fatal disease has hampered both a basic understanding of its etiology and the development of therapeutic strategies. We now report a novel model for GPS using mice deficient in a central regulatory receptor for immunoglobulin (Ig)G antibody expression and function, the type IIB Fc receptor for IgG (FcγRIIB). Mutant mice immunized with bovine C-IV reproducibly develop massive pulmonary hemorrhage with neutrophil and macrophage infiltration and crescentic glomerulonephritis. The distinctive linear, ribbon-like deposition of IgG immune complex seen in GPS was observed along the glomerular and tubulointerstitial membranes of diseased animals. These results high-light the role of FcγRIIB in maintaining tolerance and suggest that it may play a role in the pathogenesis of human GPS.

Original languageEnglish
Pages (from-to)899-905
Number of pages7
JournalJournal of Experimental Medicine
Volume191
Issue number5
DOIs
Publication statusPublished - 2000 Mar 6

Keywords

  • Alveolar/glomerular basement membrane
  • Autoimmunity
  • Fc receptor
  • Goodpasture's syndrome
  • Type IV collagen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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