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Brief Definitive Report

Fc Receptor Iib–Deficient Mice Develop Goodpasture's Syndrome upon Immunization with Type IV Collagen

Akira Nakamura^a,b,c, Takae Yuasa^a,c, Azusa Ujike^a,c, Masao Ono^a,c, Toshihiro Nukiwa^b, Jeffrey V. Ravetch^d, and Toshiyuki Takai^a,c

^a Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
^b Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan
^c Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corporation (JST), Tokyo 101-0062, Japan
^d Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021
Dept. of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Sendai 980-8575, Japan.81-22-717-850581-22-717-8501

tostakai{at}idac.tohoku.ac.jp

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 (FcRIIB). 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 highlight the role of FcRIIB in maintaining tolerance and suggest that it may play a role in the pathogenesis of human GPS.

Key Words: Goodpasture's syndrome • type IV collagen • Fc receptor • autoimmunity • alveolar/glomerular basement membrane

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