| Project/Area Number |
09470091
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TAKATSU Kiyoshi The University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (10107055)
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| Co-Investigator(Kenkyū-buntansha) |
UEHARA Shoji The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 教務職員 (60272499)
TAKAKI Satoshi The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (10242116)
KINASHI Tatsuo The University of Tokyo, Institute of Medical Science, Research Associate, 医科学研究所, 助手 (30202039)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥10,300,000 (Direct Cost: ¥10,300,000)
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| Keywords | IL-5 / B cell differentiation / CD40 / CD38 / IL-4 / Btk / X-linked immunodeficiency / Follicular mantle zone / メモリーB細胞 / 胚中心 / B細胞 / 超変異 / 抗体の親和性 / CD40とリガンド / サイトカイン |
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| Research Abstract |
Germinal center (GC) develops in secondary lymphoid tissues in response to thymus-dependent (TD) antigens (Ag). To investigate the molecular mechanism of mouse GC B cell differentiation and elucidate the function of GC B cells from X-linked immunodeficient(Xid)mice, we enriched GC B cells from spleen of TD Ag-immunized mice, monitored the expression of functional molecules, and determined the differentiation into Ag-specific IgGI antibody forming cells (AFCs) in response to anti-CD40 mAb and cytokines in vitro. GC B cells expressed IL-4 receptor (R), and approximately 5% of GC B cells expressed IL-5R.IL-4 in the presence of anti-CD40 mAb induced the differentiation of GC B cells from wild-type mice into Ag-specific IgGI AFCs, and enhanced the IL-5R expression on GC B cells from wild-type mice. IL-5 enhanced further the IgGI AFC response. The GC B cells from Xid mice responded to anti-CD40 mAb and IL-4 resulting in the IgGI response, whereas IL-5 did not enhance the response. These findings suggest that anti-CD40 mAb, IL-4, and IL-5 play a critical role in differentiation of mouse GC B cells. The GCB cells from Xid mice show functional defect with respect to IL-5-mediated differentiation.
We then examined effect of CD40 and CD38 on differentiation of GC and follicular mantle(FM)B cells. The results showed that IL-5Ralpha positive cells were mainly distributed in GC which also expressed CD40, whereas CD38 expression was down-regulated on GC B cells. Stimulation of GC B cells with IL-5 plus anti-CD38 mAb did not induce the IgGI response. The expression of IL-5Ralpha, CD38, and CD40 in Xidmice was similar to that in wild-type mice. Furthermore, IL-5Ralpha deficient mice showed normal response to TD Ag, regarding GC development and Ag-specific IgGI production. These results suggest that IL-5 plays a critical role in differentiation of mouse GC B cells as a costimulatory factor rather than an essential factor.
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