| Project/Area Number |
17591190
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2006-2007)
Kawasaki Medical School (2005) |
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Principal Investigator |
INAOKI Makoto Department of Clinical Research, National Hospital Organization Kanazawa Medical Center, Kanazawa Medical Center, Dept. of Clinical Research, Head Physician (40242549)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Wataru Kawasaki Medical School, Dept. of Dermatology, Professor (50165429)
TANAKA Ryo Kawasaki Medical School, Dept. of Dermatology, Assistant Professor (70412187)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,640,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | CD22 / aging / B lymphocytes / lymphoma |
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| Research Abstract |
CD22 is a B lymphocyte-specific response regulator that modulates B cell antigen receptor(BCR)-mediated signals. Studies have shown that CD22-deficient mice generate augmented intracellular calcium responses following BCR ligation. In addition, old CD22-deficient mice develop high-affinity autoantibodies including anti-double-strand DNA Abs. To understand further the effect of combined CD22 loss with aging on B cell development and function including autoimmunity, phenotype and histology of old CD22-deficient mice were assessed. Surprisingly, histological analysis demonstrated that half of the 15-mo-old CD22-deficient mice(7 of 14) had lymphoproliferative lesion of B cell lineage in the spleens and kidneys, whereas wild-type mice with similar age were normal. Clonality of the expanded B cells was detected by PCR analysis of rearranged Ig diversity and junction regions. Cell surface levels of IgM on mature B cells in blood, and spleen of 15-mo-old CD22-deficient mice were significantly decreased compared with those of wild-type littermates and 2-mo-old CD22-deficient mice. B cells from 15-mo-old CD22-deficient mice expressed higher levels of CD44 and MHC class II molecule I-A compared with B cells from wild-type mice. Furthermore, 15-mo-old CD22-deficient mice had significantly higher serum levels of IgM, IgG1, anti-ssDNA autoantibodies, and rheumatoid factors compared with wild-type littermates. These results suggest that BCR signaling is enhanced in old CD22-deficient mice, and combined CD22 loss with aging may predispose to development of B cell lymphoma.
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