Deletion of Fcγ Receptor IIB Renders H-2b Mice Susceptible to Collagen-induced Arthritis
| Autor: | Takae Yuasa, Azusa Ujike, Tadashi Yoshino, Toshiyuki Takai, Masao Ono, Kimio Matsumura, Jeffrey V. Ravetch, Satoshi Kubo |
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| Rok vydání: | 1999 |
| Předmět: |
musculoskeletal diseases
Immunology Type II collagen Fc receptor Arthritis macrophage FCGR2B Biology medicine.disease_cause collagen-induced arthritis Antibodies gene targeting Autoimmunity Arthritis Rheumatoid Mice Immune system Antigens CD medicine Animals Immunology and Allergy Mice Knockout Autoimmune disease Receptors IgG autoimmunity H-2 Antigens Extremities Articles medicine.disease Disease Models Animal Cartilage Macrophages Peritoneal biology.protein Cattle Collagen Antibody Interleukin-1 |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Autoimmune diseases, like rheumatoid arthritis, result from a dysregulation of the immune response culminating in hyperactivation of effector cells leading to immune-mediated injury. To maintain an appropriate immune response and prevent the emergence of autoimmune disease, activation signals must be regulated by inhibitory pathways. Biochemical and genetic studies indicate that the type IIB low-affinity receptor for immunoglobulin (Ig)G (FcgammaRIIB) inhibits cellular activation triggered through antibody or immune complexes and may be an important component in preventing the emergence of autoimmunity. To investigate the role of FcgammaRIIB in the development of type II collagen (CII)-induced arthritis (CIA), a model for rheumatoid arthritis in humans, we have examined its contribution in determining the susceptibility to CIA in the nonpermissive H-2(b) haplotype. H-2(b) mice immunized with bovine CII do not develop appreciable disease. In contrast, immunization of the FcgammaRIIB-deficient, H-2(b) mice with bovine CII induced CIA at an incidence of 42.2%. The maximal arthritis index of the FcgammaRIIB-deficient mice developing CIA (6.9 +/- 3.6) was comparable to that of DBA/1 mice (8.6 +/- 1.9), an H-2(q) strain susceptible for CIA induction. IgG1, IgG2a, and IgG2b antibody responses against CII were elevated in the FcgammaRIIB-deficient animals, especially in those mice showing arthritis, but less pronounced than DBA/1 mice. Histological examinations of the arthritic paws from FcgammaRIIB-deficient mice revealed that cartilage was destroyed and bone was focally eroded in association with marked lymphocyte and monocyte/macrophage infiltration, very similar to the pathologic findings observed in DBA/1 mice. These results indicate that a nonpermissive H-2(b) haplotype can be rendered permissive to CIA induction through deletion of FcgammaRIIB, suggesting that FcgammaRIIB plays a critical role in suppressing the induction of CIA. |
| Databáze: | OpenAIRE |
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