2002 Fiscal Year Annual Research Report

B細胞の活性化と細胞死を制御する新規遺伝子のin vivoにおける機能

Research Project

Project/Area Number	13670328
Research Institution	Chiba Cancer Center Research Institute
Principal Investigator	王継揚千葉県がんセンター, 病理研究部, 研究員 (80231041)
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)
Keywords	免疫学 / 遺伝子 / リンパ球 / アポトーシス / シグナル伝達
Research Abstract	平成14年度は、活性化B細胞で発現が抑制されるClast5遺伝子のトランスジェニックマウス(Tg)を作製し、解析を行った。Clast5-Tgでは、体重はコントロールと変わりないものの、脾臓や胸腺が小さく、脾細胞数、胸腺細胞数ともには約半分以下に減少していた。また,Clast5-Tgの胸腺においては、CD44+25+のpro-T及びCD44-25+のPre-T細胞が減少し、初期T細胞の分化、増殖が阻害されていた。骨髄ではPro-B及びPre-B細胞が明らかに減少し、初期B細胞分化が著しく障害されていることが分かった。種々の刺激に対する脾細胞の増殖反応を調べたところ、Clast5-Tgでは、CD40 ligand (CD40L),抗IgM抗体,抗CD3抗体,Con-Aなどに対する反応性が低下していた。また骨髄では、IL-7に対する反応性が低くなっていた。さらに、Clast5-TgマウスをDNP-OVAで免疫した結果、12日目の脾臓ではB220+PNA+の胚中心B細胞が減少していた。以上の結果より、Clast5は抗IgM抗体、CD40L、IL4などの刺激によりその発現が速やかに抑制されること、また、強制発現させると、B及びTリンパ球の活性化が障害されることが判明した。従って、Clast5はB及びT細胞抗原レセプターをはじめ、様々な補助刺激分子やサイトカインレセプターからのシグナルの核内ターゲットで、リンパ球の活性化を抑制するマスターレギュレーターである可能性が示唆された。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Mitsui, T., O-Wang, J.et al.: "Hypertension and angiotensin II hypersensitivity in aminopeptidase A-deficient mice"Mol. Med. (in press).
[Publications] Tada, Y., O-Wang, J.et al.: "T cell-dependent antitumor effects produced by CD4O ligand expressed on mouse lung carcinoma cells are linked with the maturation of dendritic cells and secretion of a variety of cytokines"Cancer Gene Ther.. (in press).
[Publications] Tada, Y., O-Wang, J.et al.: "Fas ligand-expressing tumors induce tumor-specific protective immunity in the inoculated hosts but vaccination with the apoptotic tumors suppresses antitumor immunity"Cancer Gene Ther.. (in press).
[Publications] Seimuya, M., O-Wang, J.et al.: "Stage-specific expression of Clast6/E3/LAPTM5 during B cell differentiation : ubiquitous expression in human B lymphomas"Int. J. Oncol.. 22. 301-304 (2003)
[Publications] Tada, Y., O-Wang, J.et al.: "A novel role for Fas ligand in facilitating antigen acquisition by dendritic cells"J. Immunal.. 169. 2241-2245 (2002)
[Publications] Bahar, R., O-Wang, J.et al.: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J. Biol. Chem.. 277. 40012-40019 (2002)
[Publications] O-Wang, J., Kajiwara, K.et al.: "An essential role for REV3 in mammalian cell survival : absence of REV3 induces p53-independent embryonic death"Biochem. Biophys. Res. Commun.. 293. 1132-1137 (2002)
[Publications] Tada, Y., O-Wang, J.et al.: "Antitumor effects are produced by forced expression of membrane-bound by not soluble Fas ligand in murine lung carcinoma cells"Anticancer. Res.. 22. 831-836 (2002)
[Publications] Seimuya, M., O-Wang, J.et al.: "Clast5/Stra13 is a negative regulator of B lymphocyte activation"Biochem. Biophys. Res. Commun.. 292. 121-127 (2002)
[Publications] Tada, Y., O-Wang, J.et al.: "Expression of the TNF-_(alpha) gene on mouse lung carcinoma cells suppresses spontaneous lung metastasis without affecting tumorigenicity"Oncology Report. 9. 585-588 (2002)
[Publications] Tada, Y., O-Wang, J.et al.: "T cell dependent and independent antitumor immunity generated by the expression of Fas ligand on mouse lung carcinoma cells"Int. J. Mol. Med.. 9. 281-285 (2002)

2002 Fiscal Year Annual Research Report

B細胞の活性化と細胞死を制御する新規遺伝子のin vivoにおける機能

Principal Investigator

王 継揚 千葉県がんセンター, 病理研究部, 研究員 (80231041)

Research Products

[Publications] Mitsui, T., O-Wang, J.et al.: "Hypertension and angiotensin II hypersensitivity in aminopeptidase A-deficient mice"Mol. Med. (in press).

[Publications] Tada, Y., O-Wang, J.et al.: "T cell-dependent antitumor effects produced by CD4O ligand expressed on mouse lung carcinoma cells are linked with the maturation of dendritic cells and secretion of a variety of cytokines"Cancer Gene Ther.. (in press).

[Publications] Tada, Y., O-Wang, J.et al.: "Fas ligand-expressing tumors induce tumor-specific protective immunity in the inoculated hosts but vaccination with the apoptotic tumors suppresses antitumor immunity"Cancer Gene Ther.. (in press).

[Publications] Seimuya, M., O-Wang, J.et al.: "Stage-specific expression of Clast6/E3/LAPTM5 during B cell differentiation : ubiquitous expression in human B lymphomas"Int. J. Oncol.. 22. 301-304 (2003)

[Publications] Tada, Y., O-Wang, J.et al.: "A novel role for Fas ligand in facilitating antigen acquisition by dendritic cells"J. Immunal.. 169. 2241-2245 (2002)

[Publications] Bahar, R., O-Wang, J.et al.: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J. Biol. Chem.. 277. 40012-40019 (2002)

[Publications] O-Wang, J., Kajiwara, K.et al.: "An essential role for REV3 in mammalian cell survival : absence of REV3 induces p53-independent embryonic death"Biochem. Biophys. Res. Commun.. 293. 1132-1137 (2002)

[Publications] Tada, Y., O-Wang, J.et al.: "Antitumor effects are produced by forced expression of membrane-bound by not soluble Fas ligand in murine lung carcinoma cells"Anticancer. Res.. 22. 831-836 (2002)

[Publications] Seimuya, M., O-Wang, J.et al.: "Clast5/Stra13 is a negative regulator of B lymphocyte activation"Biochem. Biophys. Res. Commun.. 292. 121-127 (2002)

[Publications] Tada, Y., O-Wang, J.et al.: "Expression of the TNF-_(alpha) gene on mouse lung carcinoma cells suppresses spontaneous lung metastasis without affecting tumorigenicity"Oncology Report. 9. 585-588 (2002)

[Publications] Tada, Y., O-Wang, J.et al.: "T cell dependent and independent antitumor immunity generated by the expression of Fas ligand on mouse lung carcinoma cells"Int. J. Mol. Med.. 9. 281-285 (2002)

王継揚千葉県がんセンター, 病理研究部, 研究員 (80231041)