| Project/Area Number |
06807047
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Yokohama City University |
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Principal Investigator |
SHIRAI Akira Yokohama City University School of Medicine, Assistant Professor, 医学部, 助手 (40244488)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGATSUBO Yoshiaki Yokohama City University, School of Medicine, Associate Professor, 医学部, 講師 (40137039)
MINAMI Mutsuhiko Yokohama City University, School of Medicine, Professor, 医学部, 教授 (60092342)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Superantigens / B cell activation / MHC Class II / Macrophage / Immunoglobulin / IL-6 / MCP-1 / Autoimmunity / MHCクラスII / MHCクラスII分子 / MHCクラスIIリガンド / マクロファージ活性化 |
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| Research Abstract |
It is now widely accepted that superantigens (SAgs), by binding to TCR Vb elements on T cells and to MHC class II molecules on accessory cells, stimulate T cells expressing particular TCR Vb chains. As SAg-activated T cells, having wide variety of antigen specificities, are supposed to be polyclonal by nature, they may then induce the activation of polyclonal B cells including autoreactive B cells. This possibility is now providing a basis for the hypothesis that SAgs may play important roles in the induction of autoimmune diseases.
Theoretically there are two possible mechanisms by which B cells might be polyclonally activated by SAgs ; first, SAgs stimulate B cells directly by acting as MHC class II ligands. Second, as mentioned above, SAgs stimulate B cells indirectly by virtue of their ability to mediate T/B interaction.
We first examine the direct effect of SAgs on accessory cells. The experiments using mouse macrophage cell lines and human B cell lines showed that certain bacrerial SAgs stimulated directly macrophages and B cells to secrete cytokines but that all bacterial SAgs tested inhibited Ig secretion from B cells. Next, we examine the net-effects including the direct and indirect actions of SAgs on B Cell activation. The experiments using unseparated human PBMC showed that bacterial SAg stimulated B cells to secrete Ig transienty in the early phase (3 days post stimulation) but finally inhibited the secretion by 7 days post stimulation.
In conclusion, although there still remains the possibility that superantigens may activate particular types of autoreactive B cells by specific activation of autoreactive T cells, it seems unlikely that autoreactive B cells can be activated by the mechanism of polyclonal B cell activation directly or indirectly induced by SAg stimulation.
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