| Project/Area Number |
61570312
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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 | Shimane Medical University |
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Principal Investigator |
SAKANE Tsuyoshi Shimane Medical University, 医学部, 助教授 (40127519)
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| Co-Investigator(Kenkyū-buntansha) |
KOTANI Hiroyuki Shimane Medical University, 医学部, 助手 (90135905)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Systemic lupus erythematosus / B cell hyperactivity / Polyclonal B cell activation / Resting B cells / Percoll discontinuous density gradient centrifugation / Staphylococcus aureus Cowan I / Leu 1^+ B cells / B細胞増殖因子 / Bリンパ球活性化機序 / Bリンパ球異常活性 / Staphylococcus aureus Cowan 【I】 |
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| Research Abstract |
B cell hyperactivity present in the body in patients with systemic lupus erythematosus (SLE) can be detectable via almost any measure of B cell function. Nonetheless, the basis for the B cell hyperactivity is difficult to study in vitro. Rather, the SLE B cells are more likely to hyporespond to stimuli in culture. Therefore, it remains to be determined whether SLE B cells may be endogenously hyperactive.
Peripheral blood SLE B cells contain many B cells that have been activated in vivo. However, it is necessary to isolate "genuine" resting B cells to induce B cell hyperactivity in culture. To this end, we have obtained the "genuine" resting B cells by collecting B cells sedimenting in a high density fraction on a Percoll density gradient. These B cells consist of small lymphocytes, have both IgM and IgD, do not express activation antigens, and do not proliferate spontaneously.
The resting SLE B cells proliferated in vitro at a 2 to 4 fold higher rate then normal B cells when exposed to Staphylococcus aureus Cowan I (SAC). In addition, significant proliferation was obtained after 2 days of culture in SLE patients, whereas significant response appeared 3 days after initiation of culture in normals. Moreover, the ability of the resting SLE B cells to proliferate in response to SAC was virtually identical among Leu 1^+ and Leu 1^- B cells. The results argue for a hightened excitability in a polyclonal manner of the SLE B cells to triggering stimuli as a dominant factor in the etiology of the disease. In addition to the abnormalities with B cells, excessive production of B cell growth factors is also a common feature of SLE T cells.
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