| Project/Area Number |
15590445
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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 |
Immunology
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| Research Institution | RIKEN |
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Principal Investigator |
O-WANG Jiyang RIKEN, Laboratory for Antigen Receptor Diversity, Head, 免疫多様性研究チーム, チームリーダー (80231041)
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| Co-Investigator(Kenkyū-buntansha) |
田川 雅敏 千葉県がんセンター, 病理研究部, 部長 (20171572)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | lymphocyte / differentiation / proliferation / transcription factor / apoptosis / 免疫学 / 遺伝子 / シグナル伝達 |
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| Research Abstract |
We have generated and analyzed mice that overexpress the transcription factor Clast5 in B- and T-lineage cells(Clast5-Tg). Clast5-Tg grew and bred normally and by appearance no apparent abnormality was observed. The sizes and body weights of Clast5-Tg were not different from age- and sex-matched littermates. Remarkably, spleen and thymus sizes of Clasti5-Tg were apparently reduced compared to control littermates. The cell numbers in these organs were also significantly decreased. There was a decrease of pro-T and pre-T cells in the thymus and pro-B and pre-B cells in the bone marrow of Clast5-Tg mice, suggesting that Clast5 functions to inhibit the expansion of early T and B cells. Mature B cells of Clast5-Tg exhibited a reduced responsiveness to antigen receptor crosslinking and also had a mild reduction in the antibody production against a T-dependent antigen. These results collectively indicate that Clast5 is a negative regulator for both early B and T cell development and late B cell activation and differentiation. In collaboration with Dr.Taneja at Mount Sinai University, we also analyzed B cell function in Clast5-deficient mice. Although Clast5-deficiency had a mild effect on early B cell differentiation in the bone marrow, Clast5-deficient mature B cells exhibited normal responses to a variety of external stimuli, including antigen receptor crosslinking and CD40 ligation. These results suggest that while Clast5 plays a crucial role in B cell differentiation and activation, mature B cells may express another inhibitory factor that can compensate for the function of Clast5.
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