| Budget Amount *help |
¥3,980,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. Although autoantibody production correlates with skin sclerosis, a direct role for B lymphocytes in disease development or progression has remained controversial. To address this issue, skin sclerosis and autoimmunity was assessed in tight-skin mice, a genetic model of human systemic sclerosis, following circulating and tissue B cell depletion using an anti-mouse CD20 mAb before and after disease development. CD20 mAb treatment (10-20 rig) depleted the majority (85-99%) of circulating and tissue B cells in newborn and adult tight-skin mice. Dose-dependent B cell depletion in newborn tight-skin mice significantly suppressed (-43%) the development of skin fibrosis and hypergammaglobulinemia, and abrogated rheumatoid factor and autoantibody production. B cell depletion in young tight-skin mice also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin and spleen. By contrast, effective B cell depletion did not affect skin fibrosis, hypergammaglobulinemia, rheumatoid factor and autoantibody levels in adult mice with established disease. Thereby, B cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.
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