| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Research Abstract |
Keratin 5 (K5) is a cytoskeletal tissue-specific protein expressed in the epithelial cells of skin and esophagus. Although K5 is also expressed in lymphoid organs such as thymus, ectopic K5 expression in lymphocytes has never been reported. Since K5 expression in epidermal keratinocytes is transient during epidermal differentiation, not all keratinocytes express K5. Here we demonstrate an ectopic epidermal self-protein expression in a part of B-1 B cell by fate mapping of K5-expressing cells. K5-Cre ×CAG-CAT-loxP-EGFP double transgenic (K5×GFP) mice that express enhanced green fluorescence protein (GFP) under the control of the K5 promoter were employed. Unexpectedly, B220^+GFP^+cells were found in lymph nodes (LNs), spleen, peripheral blood, and peritoneum. These cells were located in a non-follicular area of secondary lymph organs and were IgM+IgDlowCD23^-CD43^+CD19^+CD93^-, indicating that they were B-1 B cells, which are the major B cell subpopulation in the pleural and peritoneal cavities. Although GFP+B-1 cells did not express K5 in the periphery, LinCD93^+B220low-negCD19^+B^-1 B cell progenitors expressed GFP and B220^+CD93^+progenitor cells expressed K5 and MHC^-class II in bone marrow (BM), indicating that GFP^+B^-1 cells transiently expressed K5 and the progenitor cells were potential antigen-presenting cells. Interestingly, GFP+B^-1 cells in the periphery continued expressing MHC class II and had exogenous antigen-presentingcapacity comparable to non-follicular B cells and plasmacytoid dendritic cells. GFP^+B^-1 cells proliferated more rapidly in vivo and spontaneously secreted more IgM than GFPB-1 cells in vitro. These results indicate that a part of B-1 B cells transiently express K5 in BM and are potent for both natural antibody production and antigen presentation.
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