免疫システム構築の情報伝達制御

2002 Fiscal Year Annual Research Report

• 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 東京医科歯科大学, 大学院・医歯学総合研究科, 客員教授 (90027095)
• Keywords: B細胞分化 / T細胞分化 / リンパ球前駆細胞

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、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。(1)ノックアウトマウスの作製に最適なgermline transmissionに優れたES細胞を樹立選別し、未分化状態に維持に必要な至適培養条件を見いだし、最良のES細胞の供給をおこなった。(2)DNAシークエンス決定支援をおこなった。(3)細胞培養に最適な牛胎児血清を選別し、培養条件の標準化、均一化をはかった。(4)ハイブリドーマなど共有細胞株の保存管理と供給をおこなった。(5)遺伝子改変動物の樹立と系統維持、供給をおこなった。このように研究支援体制を強化継続したことにより、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みいだし、その成果は国際雑誌に数多く発表することができた。さらに2003年2月20-23日に、3年間の研究の総括と成果発表・討論のため、海外の一流研究者を交えて、International Symposium on Regulation of Immune Response in Heath and Diseaseを開催した。

Research Products

• [Publications] Obata, S., et al.: "Overexpression of the c-fos gene perturbs functional maturation of M1 cells into macrophages"Mol. Immunol.. 39. 585-594 (2003)
• [Publications] Sasagawa, K., et al.: "Identification of Nd1, a novel murine kelch family protein, involved in stabilization of actin filaments"J. Biol. Chem.. 277. 44140-44146 (2002)
• [Publications] Bahar, R., et al.: "Growth retardation, polyploidy and multinucleation induced by Clast3, a novel cell cycle-regulated protein"J. Biol. Chem.. 277. 40012-40019 (2002)
• [Publications] Yoshida, T., et al.: "Activation of STAT3 by the Hepatitis C virus core protein leads to cellular transformation"J. Exp. Med.. 196. 641-653 (2002)
• [Publications] Nakagawa, Y., et al.: "Downregulation of bcl-xL is relevant to UV-induced apoptosis in fibroblasts"J. Biochem. Mol. Biol.. 35. 452-458 (2002)
• [Publications] Toyama, H., et al.: "Memory B cells without somatic hypermutation are generateded from Bcl6-deficient B cells"Immunity. 17. 329-339 (2002)
• [Publications] Tada, Y., et al.: "A novel role for Fas ligand in facilitating antigen acquisition by dendritic cells"J. Immunol.. 169. 2241-2245 (2002)
• [Publications] Arima, M., et al.: "A putative silencer element in the IL-5 gene recognized by Bcl6"J. Immunol.. 169. 829-836 (2002)
• [Publications] Ichii, H., et al.: "Role for Bcl-6 in the generation and maintenance of memory CD8^+ T cells"Nature Immunol.. 3. 558-563 (2002)
• [Publications] Hikita, S., et al.: "Overexpression of TIAP/m-survivin in thymocytes enhances cell proliferation"Mol. Immunol.. 39. 289-298 (2002)
• [Publications] Oshitari, T., et al.: "Suppression of c-fos mediates inhibition of cell death and increases neurite regeneration in retinal ganglion cells"Invest. Ophtalm. Vis. Sci.. 43. 2442-2449 (2002)
• [Publications] Sakashita, C., et al.: "Cloning and characterization of the human BAZF gene, a homologue of the BCL6 oncogene"Biochem. Biophys. Res. Commun.. 291. 567-573 (2002)
• [Publications] Kojima, S., et al.: "Histological analysis of vaginal opening and spermatogenesis in Bcl6-deficient mice"Jpn. J. Fertil. Steril.. 47. 39-45 (2002)
• [Publications] Sata, M., et al.: "Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis"Nature Med.. 8. 403-409 (2002)
• [Publications] Seimiya, M., et al.: "Clast5/Stra13 is a negative regulator of B lymphocyte activation"Biochem. Biophys. Res. Commun.. 292. 121-127 (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] Hamada, H., et al.: "Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine"The Journal of Immunology. 168. 57-64 (2002)
• [Publications] Nishiyama, Y., et al.: "Homeostatic regulation of intestinal villous epithelia by B lymphocytes"The Journal of Immunology. 168. 2626-2633 (2002)
• [Publications] Onai, N., et al.: "Pivotal role of CCL25 (TECK)/CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes"International Immunology. 14. 687-694 (2002)
• [Publications] Murai, M., et al.: "Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction"Nature Immunology. 4. 154-160 (2003)
• [Publications] Lu, M., et al.: "The common myelolymphoid progenitor : A key intermediate stage in hemopoiesis generating T and B cells"J. Immunol.. 169. 3519-3525 (2002)
• [Publications] Kawamoto, H., et al.: "Extensive proliferation of T cell lineage restricted progenitors in the thymus : An essential process for clonal expression of diverse T cell receptor beta chains"Eur. J. Immunol.. 33(in press). (2003)
• [Publications] Ueno, T., et al.: "Role for CCR7 ligands in the emigration of newly generated T lymphocytes from the neonatal thymus"Immunity. 16. 205-218 (2002)
• [Publications] Akamatsu, Y., et al.: "Deletion of the RAG2 C-terminus leads to impaired lymphoid development in mice"Proc. Natl. Acad. Sci. USA. 100. 1209-1214 (2003)
• [Publications] Wang, Y-H., et al.: "Differential surrogate light chain expression governs B cell differentiation"Blood. 99. 2459-2467 (2002)
• [Publications] Taguchi, T., et al.: "Pre-BCR-mediated signal inhibits CD24-induced apoptosis in human pre-B cells"J. Immunol.. 170. 252-260 (2003)
• [Publications] Kubo, S., et al.: "Long-term maintenance of IgE-mediated memory in mast cells in the absence of detectable serum IgE"J. Immunol.. 170. 775-780 (2003)
• [Publications] Sato, E., et al.: "Chronic inflammation in skin can be induced in IgE transgenic mice by a single challenge of multivalent antigen"J. Allergy Clin. Immunol.. 111. 143-148 (2003)
• [Publications] Saijo, K., et al.: "Essential role of Src-family protein tyrosine kinases in NF-κB activation during B cell development"Nature Immunol.. 4. 274-279 (2003)
• [Publications] Tsuchiya, K., et al.: "Molecular cloning and characterization of TPP36 and its isoform TPP32, novel substrates of Abl tyrosine kinase"FEBS lett.. 537. 203-209 (2003)
• [Publications] 烏山 一: "プレB細胞レセプターを介するB細胞分化誘導"蛋白質核酸酵素増刊号. 47. 2182-2187 (2002)
• [Publications] 烏山 一: "B細胞発生・分化の分子制御機構とその破綻"感染炎症免疫. 32. 18-27 (2002)
• [Publications] Wiltshire, C., et al.: "A new c-Jun N-terminal kinase (JNK)-interacting protein Sab(SH3BP5), associates with mitochondria"Biochem J.. 367. 577-585 (2002)
• [Publications] Agematsu, K., et al.: "Absence of memory B cells in patients with common variable immunodeficiency"Clin Immunol.. 103. 34-42 (2002)
• [Publications] Inabe, K., et al.: "Bruton's tyrosine kinase regulates B cell antigen receptor-mediated JNK1 response through Rac1 and phospholipase C-gamma2 activation"FEBS Lett.. 514. 260-262 (2002)
• [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.. 81. 211-216 (2002)
• [Publications] Han, H., et al.: "Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision"Int. Immunol.. 14. 637-645 (2002)
• [Publications] Watanabe, N., et al.: "Activation and differentiation of autoreactive B-1 cells by interleukin-10 induce autoimmune hemolytic anemia in Fas-deficient anti-erythrocyte immunoglobulin transgenic mice"J. Exp. Med.. 196. 141-146 (2002)
• [Publications] Lahn, M., et al.: "MHC class I-dependent Vγ4^+ pulmonary T cells regulate αβ T cell-independent airway responsiveness"Proc. Natl. Acad. Sci. USA.. 99. 8850-8855 (2002)
• [Publications] Wang, J.W., et al.: "Influence of SHIP on the NK repertoire and allogeneic bone marrow transplantation"Science. 15. 2094-2097 (2002)
• [Publications] 反町典子: "NK細胞の系統発生-missing self認識の起源を求めて 動物界における免疫系の進化 別冊医学のあゆみ"医歯薬出版株式会社. 5 (2002)
• [Publications] 反町典子: "抑制性レセプターによる細胞接着制御 蛋白質核酸酵素増刊号 免疫研究の最前線"共立出版. 5 (2002)
• [Publications] 反町典子: "NKレセプターファミリー分,CD94とLy49Qの機能 Molecular Medicine増刊号 免疫2002"中山書店. 9 (2002)
• [Publications] 南野昌信, 石川博通: "粘膜免疫学の最前線 粘膜リンパ球の発達分化"医薬ジャーナル社. 11 (2002)
• [Publications] 南野昌信, 石川博通: "胸腺外T細胞の発達・分化 標準免疫学 第2版"医学書院. 8 (2002)
• [Publications] Katsura, Y., Kawamoto, H.: "A new clonal assay system for lymphoid and myeloid lineages"Margaret H. Baron (Humana Press) (In Press). (2003)
• [Publications] Ueno, T., et al.: "Basic Cell Culture Protocols"Humana Press, NJ, USA (in press). (2003)
• [Publications] 烏山 一: "「B細胞の初期分化」標準免疫学第2版(谷口克、宮坂昌之編)"医学書院. 9 (2002)