2001 Fiscal Year Annual Research Report

免疫システム構築の情報伝達制御

Research Project

Project/Area Number	12051103
Research Institution	Tokyo Medical and Dental University
Principal Investigator	烏山一東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (60195013)
Co-Investigator(Kenkyū-buntansha)	徳久剛史千葉大学, 大学院・医学研究科, 教授 (20134364) 桂義元京都大学, 再生医学研究所, 教授 (90027095)
Keywords	B細胞分化 / T細胞分化 / リンパ球前駆細胞 / 胚中心 / 遺伝子再構成
Research Abstract	「リンパ球の初期分化を誘導・制御するシグナル伝達機構」「リンパ球の系列分岐・運命分岐を決定するシグナル伝達機構」「末梢リンパ組織における免疫系再構築のシグナル伝達機構」を研究課題とする3つの計画研究を設定して、8名の計画研究班員と15名の公募研究班員によって研究を遂行した。本調整班では、研究グループ間の連絡調整・情報交換、共通機器の購入、実験条件の統一のための共通試薬等の検定・購入等をおこない、効率よい研究推進のための支援体制強化につとめた。その一環として-150℃超低温保存槽を購入し、ノックアウトマウスの作製に必須な優良なES細胞ならびにフィーダー細胞、各種リンコンビナント・サイトカインを大量分泌する遺伝子導入細胞株、特異抗体を産生する各種ハイブリドーマなど多くの研究者が共通に必要とする細胞株を一括して保存管理し、研究者の要請に即座に応じられる体制を整えた。また、実験条件統一の一環として、胸腺臓器培養・胎児肝臓器培養やストローマ細胞上での細胞培養の条件検討、最適な牛胎児血清ロットなど共通研究試薬の選定をおこなった。さらにノックアウトマウスやトランスジェニックマウスなどの遺伝子改変動物の作製に必須な優れたES細胞の樹立選別、共通マウスの系統維持、遺伝子解析などの研究支援体制を強化した。このような研究支援体制を整えたことにより、免疫システム構築の情報伝達制御機構に関して多くの新知見を得ることができた。

Research Products

(47 results)

All Other

All Publications (47 results)

[Publications] Kojima, S., et al.: "Disruption of the Bcl6 gene increases testicular germ cell apoptosis in mice"Development. 128. 57-65 (2001)
[Publications] Zhang, H., et al.: "A novel functional domain of Bc16 family that recruits histone deacethylases"Biochim.Biophys.Acta. 1543. 188-200 (2001)
[Publications] Bannai, M. et al.: "Abundance of unconventional CD8(+) natural killer T cells in the large intestine"Eur.J.Immunol.. 31. 3361-3369 (2001)
[Publications] Mizushima, N., et al.: "Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells"J.Cell Biol.. 152. 657-668 (2001)
[Publications] Hamada, H. et al.: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"J.Immunol.. 168. 57-64 (2002)
[Publications] Murasawa, M., et al.: "GL7 defines the cycling stage of pre-B cells in murine bone marrow"Eur.J.Immunol.. 32. 291-298 (2002)
[Publications] Ikawa, T., et al.: "Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2"Proc.Natl.Acad.Sci.USA. 98. 5164-5169 (2001)
[Publications] Ohmura, K., et al.: "Immature multipotent hematopoietic progenitors lacking long-term bone marrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses"J.Immunol.. 166. 3290-3296 (2001)
[Publications] Shimizu, C., et al.: "Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity"Int.Immunol.. 13. 105-117 (2001)
[Publications] Egawa, T., et al.: "The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor"Immunity. 15. 1-20 (2001)
[Publications] Yoshida, H., et al.: "Expression of a4b7 intergrn defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells"J.Immunol.. 167. 2511-2521 (2001)
[Publications] Itoi, M., et al.: "Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage"Int.Immunol.. 13. 1203-1211 (2001)
[Publications] Katsura, Y.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis"Int.Rev.Immunol.. 20. 1-20 (2001)
[Publications] Katsura, Y., et al.: "Redefinition of lymphoid progenitors"Nature Rev.Immunol.. 2. 127-132 (2002)
[Publications] Ueno, T., et al.: "Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus"Immunity. (in press). (2002)
[Publications] Yoh, K., et al.: "Transgenic overexpression of MafK suppresses T cell proliferation and function in vivo"Genes to Cells. 6. 1055-1066 (2001)
[Publications] Tada M., et al.: "Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells"Current Biology. 11. 1553-1558 (2001)
[Publications] Sano, S., et al.: "Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)
[Publications] Masuyama, N., et al.: "Akt inhibits the orphan nuclear receptor Nur77 and T cell apoptosis"J.Biol.Chem.. 276. 32799-32805 (2001)
[Publications] Takahama, Y.: "Genetic modulation of immature T lymphocytesand its application"J.Med.Invest.. 48. 25-30 (2001)
[Publications] Toyama-Sorimachi, N., et al.: "Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and delivers inhibitory signals independent of Ly-49"J.Immunol.. 166. 3771-3779 (2001)
[Publications] Kouro, T., et al.: "Bruton's tyrosine kinase (Btk) is required for signaling the CD79b-mediated pro-B to pre-B cell transition"Int.Immunol.. 13. 485-493 (2001)
[Publications] Agematsu, K., et al.: "Complete arrest from pro-to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations"Clin.Exp.Immunol.. 124. 461-464 (2001)
[Publications] Kinoshita, T., et al.: "Oncostatin M suppresses generation of lymphoid progenitors in fetal liver by inhibiting the hepatic microenvironment"Exp.Hematol.. 299. 1091-1097 (2001)
[Publications] Kubo, S., et al.: "Drastic up-regulation of high affinity IgE receptor on mast cells is induced by IgE binding through stabilization and accumulation of the receptor on the cell surface"J.Immunol.. 167. 3427-3434 (2001)
[Publications] Stephan, R.P.: "Analysis of VpreB expression during B lineage differentiation in lambda5-deficient mice"J Immunol. 167. 3734-3739 (2001)
[Publications] Wang, Y-H., et al.: "Differential surrogate light chain expression governs B cell differentiation"Blood. (in press). (2002)
[Publications] Honda, K., et al.: "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis"J.Exp.Med.. 193. 621-630 (2001)
[Publications] Agata, Y., et al.: "Histone acetylation determines the developmentally regulated accessibility for T cell receptor-γ gene recombination"J.Exp.Med.. 193. 873-879 (2001)
[Publications] Lee, H.-C., et al.: "Induction of germline transcription in the human T cell receptor γ locus by STAT5"J.Immunol. 167. 320-326 (2001)
[Publications] Ohba, Y., et al.: "Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis"EMBO J. 20. 3333-3341 (2001)
[Publications] Ye, S.-K., et al.: "Differential roles of cytokine receptors in the development of epidermal γ δ T Cells"J.Immunol.. 167. 1929-1934 (2001)
[Publications] Fagarasan, S., et al.: "In situ class switching and differentiation to IgA-producing cells in the gut lamina propria"Nature. 413. 639-643 (2001)
[Publications] Ye, S.-K., et al.: "The IL-7 receptor controls the accessibility of the TCR γ locus by Stat5 and histone acetylation"Immunity. 15. 813-823 (2001)
[Publications] Lee, H.-C., et al.: "Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice"Immunol.Lett.. (In press). (2002)
[Publications] Sakamoto, M., et al.: "Maternal germline mosaicism of X-linked agammaglobulinemia"Am.J.Med.Genet.. 99. 234-237 (2001)
[Publications] Baba, Y. et al.: "BLNK mediates Syk-dependent Btk activation"Proc.Natl.Acad.Sci.USA.. 98. 2582-2586 (2001)
[Publications] Usui, K., et al.: "Reccurent pneumonia with mild hypogammaglobulinemia diagnosed as X-linked agammaglobulinemia in adults"Respir.Res.. 2. 188-192 (2001)
[Publications] Joe, EK., et al.: "Characterization of mutations, including a novel regulatory defect in the first intron, in Bruton's tyrosine kinase (Btk) gene from seven Korean X-linked agammaglobulinemia families"J.Immunol.. 167. 4038-4045 (2001)
[Publications] Tsukada, S., et al.: "Btk and BLNK in B cell development"Adv.Immunol.. 77. 123-162 (2001)
[Publications] Kanegane, H., et al.: "Clinical and genetic characteristics of hypogammaglobulinemic males with Btk mutations detected by flow cytometric assay combined with genetic analysis"J.Allergy.Clin.Immunol.. 108. 1012-1020 (2001)
[Publications] Futatani, T., et al.: "Bruton's tyrosine kinase is present in normal platelets and its absence identifies patients with X-linked agammaglobulinemia and carrier females"Br.J.Haematol.. 114. 141-149 (2001)
[Publications] Wang, Y., et al.: "Bruton's tyrosine kinase gene mutations in Turkish patients wuth presumed X-linked agammaglobulinemia"Hum.Mutat.. 18. 356 (2001)
[Publications] Watanabe, D., et al.: "Four tyrosine residues in phospholipase C-gamma2, identified as Btk-dependent phodphorylation sites, are required for B cell antigen receptor-coupled calcium signaling"J.Biol.Chem.. 276. 38595-38601 (2001)
[Publications] Wang, J.-W., et al.: "SHIP influences the NK repertoire and allogeneic marrow transplantation"Science. (in press). (2002)
[Publications] Toyama-Sorimachi, N., et al.: "Activating and inhibitory immunoglobulin-like receptors"Springer-Verlag(分担分). 5 (2001)
[Publications] Maki, K., et al.: "Activating and inhibitory immunoglobulin-like receptors"Springer-Verlag(分担分). 6 (2001)

2001 Fiscal Year Annual Research Report

免疫システム構築の情報伝達制御

Principal Investigator

烏山 一 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (60195013)

Research Products

[Publications] Kojima, S., et al.: "Disruption of the Bcl6 gene increases testicular germ cell apoptosis in mice"Development. 128. 57-65 (2001)

[Publications] Zhang, H., et al.: "A novel functional domain of Bc16 family that recruits histone deacethylases"Biochim.Biophys.Acta. 1543. 188-200 (2001)

[Publications] Bannai, M. et al.: "Abundance of unconventional CD8(+) natural killer T cells in the large intestine"Eur.J.Immunol.. 31. 3361-3369 (2001)

[Publications] Mizushima, N., et al.: "Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells"J.Cell Biol.. 152. 657-668 (2001)

[Publications] Hamada, H. et al.: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"J.Immunol.. 168. 57-64 (2002)

[Publications] Murasawa, M., et al.: "GL7 defines the cycling stage of pre-B cells in murine bone marrow"Eur.J.Immunol.. 32. 291-298 (2002)

[Publications] Ikawa, T., et al.: "Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2"Proc.Natl.Acad.Sci.USA. 98. 5164-5169 (2001)

[Publications] Ohmura, K., et al.: "Immature multipotent hematopoietic progenitors lacking long-term bone marrow-reconstituting activity in the aorta-gonad-mesonephros region of murine day 10 fetuses"J.Immunol.. 166. 3290-3296 (2001)

[Publications] Shimizu, C., et al.: "Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity"Int.Immunol.. 13. 105-117 (2001)

[Publications] Egawa, T., et al.: "The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor"Immunity. 15. 1-20 (2001)

[Publications] Yoshida, H., et al.: "Expression of a4b7 intergrn defines a distinct pathway of lymphoid progenitors committed to T cells, fetal intestinal lymphotoxin producer, NK, and dendritic cells"J.Immunol.. 167. 2511-2521 (2001)

[Publications] Itoi, M., et al.: "Two distinct steps of immigration of hematopoietic progenitors into the early thymus anlage"Int.Immunol.. 13. 1203-1211 (2001)

[Publications] Katsura, Y.: "Stepwise lineage restriction of progenitors in lympho-myelopoiesis"Int.Rev.Immunol.. 20. 1-20 (2001)

[Publications] Katsura, Y., et al.: "Redefinition of lymphoid progenitors"Nature Rev.Immunol.. 2. 127-132 (2002)

[Publications] Ueno, T., et al.: "Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus"Immunity. (in press). (2002)

[Publications] Yoh, K., et al.: "Transgenic overexpression of MafK suppresses T cell proliferation and function in vivo"Genes to Cells. 6. 1055-1066 (2001)

[Publications] Tada M., et al.: "Nuclear reprogramming of somatic cells by in vitro hybridization with ES cells"Current Biology. 11. 1553-1558 (2001)

[Publications] Sano, S., et al.: "Stat3 in thymic epithelial cells is essential for postnatal maintenance of thymic architecture and thymocyte survival"Immunity. 15. 261-273 (2001)

[Publications] Masuyama, N., et al.: "Akt inhibits the orphan nuclear receptor Nur77 and T cell apoptosis"J.Biol.Chem.. 276. 32799-32805 (2001)

[Publications] Takahama, Y.: "Genetic modulation of immature T lymphocytesand its application"J.Med.Invest.. 48. 25-30 (2001)

[Publications] Toyama-Sorimachi, N., et al.: "Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and delivers inhibitory signals independent of Ly-49"J.Immunol.. 166. 3771-3779 (2001)

[Publications] Kouro, T., et al.: "Bruton's tyrosine kinase (Btk) is required for signaling the CD79b-mediated pro-B to pre-B cell transition"Int.Immunol.. 13. 485-493 (2001)

[Publications] Agematsu, K., et al.: "Complete arrest from pro-to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations"Clin.Exp.Immunol.. 124. 461-464 (2001)

[Publications] Kinoshita, T., et al.: "Oncostatin M suppresses generation of lymphoid progenitors in fetal liver by inhibiting the hepatic microenvironment"Exp.Hematol.. 299. 1091-1097 (2001)

[Publications] Kubo, S., et al.: "Drastic up-regulation of high affinity IgE receptor on mast cells is induced by IgE binding through stabilization and accumulation of the receptor on the cell surface"J.Immunol.. 167. 3427-3434 (2001)

[Publications] Stephan, R.P.: "Analysis of VpreB expression during B lineage differentiation in lambda5-deficient mice"J Immunol. 167. 3734-3739 (2001)

[Publications] Wang, Y-H., et al.: "Differential surrogate light chain expression governs B cell differentiation"Blood. (in press). (2002)

[Publications] Honda, K., et al.: "Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer's patch organogenesis"J.Exp.Med.. 193. 621-630 (2001)

[Publications] Agata, Y., et al.: "Histone acetylation determines the developmentally regulated accessibility for T cell receptor-γ gene recombination"J.Exp.Med.. 193. 873-879 (2001)

[Publications] Lee, H.-C., et al.: "Induction of germline transcription in the human T cell receptor γ locus by STAT5"J.Immunol. 167. 320-326 (2001)

[Publications] Ohba, Y., et al.: "Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis"EMBO J. 20. 3333-3341 (2001)

[Publications] Ye, S.-K., et al.: "Differential roles of cytokine receptors in the development of epidermal γ δ T Cells"J.Immunol.. 167. 1929-1934 (2001)

[Publications] Fagarasan, S., et al.: "In situ class switching and differentiation to IgA-producing cells in the gut lamina propria"Nature. 413. 639-643 (2001)

[Publications] Ye, S.-K., et al.: "The IL-7 receptor controls the accessibility of the TCR γ locus by Stat5 and histone acetylation"Immunity. 15. 813-823 (2001)

[Publications] Lee, H.-C., et al.: "Seeding of dendritic epidermal T cells in the neonatal skin is reduced in 129 strain of mice"Immunol.Lett.. (In press). (2002)

[Publications] Sakamoto, M., et al.: "Maternal germline mosaicism of X-linked agammaglobulinemia"Am.J.Med.Genet.. 99. 234-237 (2001)

[Publications] Baba, Y. et al.: "BLNK mediates Syk-dependent Btk activation"Proc.Natl.Acad.Sci.USA.. 98. 2582-2586 (2001)

[Publications] Usui, K., et al.: "Reccurent pneumonia with mild hypogammaglobulinemia diagnosed as X-linked agammaglobulinemia in adults"Respir.Res.. 2. 188-192 (2001)

[Publications] Joe, EK., et al.: "Characterization of mutations, including a novel regulatory defect in the first intron, in Bruton's tyrosine kinase (Btk) gene from seven Korean X-linked agammaglobulinemia families"J.Immunol.. 167. 4038-4045 (2001)

[Publications] Tsukada, S., et al.: "Btk and BLNK in B cell development"Adv.Immunol.. 77. 123-162 (2001)

[Publications] Kanegane, H., et al.: "Clinical and genetic characteristics of hypogammaglobulinemic males with Btk mutations detected by flow cytometric assay combined with genetic analysis"J.Allergy.Clin.Immunol.. 108. 1012-1020 (2001)

[Publications] Futatani, T., et al.: "Bruton's tyrosine kinase is present in normal platelets and its absence identifies patients with X-linked agammaglobulinemia and carrier females"Br.J.Haematol.. 114. 141-149 (2001)

[Publications] Wang, Y., et al.: "Bruton's tyrosine kinase gene mutations in Turkish patients wuth presumed X-linked agammaglobulinemia"Hum.Mutat.. 18. 356 (2001)

[Publications] Watanabe, D., et al.: "Four tyrosine residues in phospholipase C-gamma2, identified as Btk-dependent phodphorylation sites, are required for B cell antigen receptor-coupled calcium signaling"J.Biol.Chem.. 276. 38595-38601 (2001)

[Publications] Wang, J.-W., et al.: "SHIP influences the NK repertoire and allogeneic marrow transplantation"Science. (in press). (2002)

[Publications] Toyama-Sorimachi, N., et al.: "Activating and inhibitory immunoglobulin-like receptors"Springer-Verlag(分担分). 5 (2001)

[Publications] Maki, K., et al.: "Activating and inhibitory immunoglobulin-like receptors"Springer-Verlag(分担分). 6 (2001)

烏山一東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (60195013)