Regulation of B-cell proliferation and differentiation by reorganization of receptor-signal transduction machinery.

• Project/Area Number: 19390141
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo University of Science
• Principal Investigator: DAISUKE Kitamura Tokyo University of Science, 生命科学研究所, 教授 (70204914)
• Co-Investigator(Kenkyū-buntansha): 白鳥 行大 東京理科大学, 生命科学研究所, 助教 (90379090) ; 野嶋 卓也 東京理科大学, 生命科学研究所, 助教 (10434036)
• Co-Investigator(Renkei-kenkyūsha): IKUO Shiratori 東京理科大学, 生命科学研究所, 助教 (90379090) ; NOJIMA TAKUYA 東京理科大学, 生命科学研究所, 助教 (10434036)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: シグナル伝達 / 細胞増殖 / B 細胞分化 / B リンパ球 / 免疫学 / 抗原受容体 / プレB 細胞レセプター / B細胞分化 / Bリンパ球 / プレB細胞レセプター

Research Abstract

プレB・B細胞の分化・増殖に伴う多様なイベントを引き起こすシグナルはpre-BCR・BCRから単一のIgα/βを介して細胞内に送られるので、多様な細胞内シグナル伝達系が想定される。この多様性はBLNKを含む限られた数のシグナル伝達因子の分化段階や活性化状態の変遷に応じた再構成によって創出されることが示唆された。すなわち、BLNKの機能がpre-BCR・BCRの下流で増殖の誘導から抑制へと転換する再構成の分子機構が明らかになった。

Research Products

• [Journal Article] Possible contribution of DNase γ to immunoglobulin V gene diversification (2009)
  • Author(s): Okamoto, N., Okamoto, M., Araki, S., Arakawa, H., Mizuta, R. and Kitamura, D.
  • Journal Title: Immunol. Lett. (in press)
  • Peer Reviewed
• [Journal Article] BLNK binds active H-Ras to promote B cell receptor-mediated capping and ERK activation (2009)
  • Author(s): Imamura, Y., Oda, A., Katahira, T., Bundo, K., Pike, K.A., Ratcliffe, M.J.H. and Kitamura, D.
  • Journal Title: J. Biol. Chem. 284 Pages: 9804-9813
  • Peer Reviewed
• [Journal Article] BLNK suppresses pre-B cell leukemogenesisthrough inhibition of JAK3 (2009)
  • Author(s): Nakayama, J., Yamamoto, M., Hayashi, K., Satoh, H., Bundo, K., Kubo, M., Goitsuka, R., Farrar, M. A. and Kitamura D.
  • Journal Title: Blood 113 Pages: 1483-1492
  • Peer Reviewed
• [Journal Article] BLNK suppresses pre-B cell leukemogenesis through inhibition of JAK3. (2009)
  • Author(s): Joji Nakayama
  • Journal Title: Blood 113 Pages: 1483-1492
  • Peer Reviewed
• [Journal Article] Hematopoietic lineage cell-specific protein-1 (HS1) regulates PAR-mediated ERK activation and thromboxane generation in platelets (2008)
  • Author(s): Kahner, B. N., Dorsam, R. T., Kim, S., Shankar, H., Kitamura, D., Kunapuli, S. P.
  • Journal Title: Platelets 19 Pages: 614-623
  • Peer Reviewed
• [Journal Article] PKCη directs induction of IRF-4 expression and Ig κ gene rearrangement in pre-BCR signaling pathway (2008)
  • Author(s): Oda, A., Ono, T., Yamamoto, M., Goitsuka, R. and Kitamura, D.
  • Journal Title: Int. Immunol 20 Pages: 1417-1426
  • NAID: 10024357764
  • Peer Reviewed
• [Journal Article] Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals (2008)
  • Author(s): Shinohara, M., Koga, T., Okamoto, K., Sakaguchi, S., Arai, K., Yasuda, H., Takai, T., Kodama, T., Morio, T,. Geha, R. S., Kitamura, D., Kurosaki, T., Ellmeier, W. and Takayanagi, H.
  • Journal Title: Cell 132 Pages: 794-806
  • Peer Reviewed
• [Journal Article] Distinct regulatory functions of SLP-76 and MIST in NK cell cytotoxicity and IFN-γ production (2008)
  • Author(s): Hidano, S., Sasanuma, H., Ohshima, K., Seino, K.-I., Kumar, L., Hayashi, K., Hikida, M., Kurosaki, T., Taniguchi, M., Geha, R. S., Kitamura, D. and Goitsuka, R.
  • Journal Title: Int. Immunol 20 Pages: 345-352
  • NAID: 10021239822
  • Peer Reviewed
• [Journal Article] Hematopoietic lineage cell-specific protein-1 (HS1) regulates PAR-mediated ERK activation and thromboxane generation in platelets. (2008)
  • Author(s): Bryan N. Kahner
  • Journal Title: Platelets 19 Pages: 614-623
  • Peer Reviewed
• [Journal Article] PKCη directs induction of IRF-4 expression and Ig κ gene rearrangement in pre-BCR signaling pathway. (2008)
  • Author(s): Akihisa Oda
  • Journal Title: International Immunology 20 Pages: 1417-1426
  • Peer Reviewed
• [Journal Article] Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. (2008)
  • Author(s): Masahiro Shinohara
  • Journal Title: Cell 132 Pages: 794-806
  • Peer Reviewed
• [Journal Article] Chicken cathelicidin-B1, an antimicrobial guardian at the mucosal M cell gateway (2007)
  • Author(s): Goitsuka, R., Chen, C.L., Benyon, L., Asano, Y., Kitamura, D. and Cooper, M.D.
  • Journal Title: Proc. Natl. Acad. Sci.USA. 104 Pages: 15063-15068
  • Peer Reviewed
• [Journal Article] Hematopoietic lineage cell specific protein 1 (HS1) is a functionally important signaling molecule in platelet activation (2007)
  • Author(s): Kahner, B.N., Dorsam, R.T., Mada, S.R., Kim, S., Stalker, T.J., Brass, L.F., Daniel, J.L., Kitamura, D. and Kunapuli, S.P.
  • Journal Title: Blood 110 Pages: 2449-2456
  • Peer Reviewed
• [Journal Article] Stage-specific expression of DNase gamma during B-cell development and its role in B-cell receptor-mediated apoptosis in WEHI-231 cells (2007)
  • Author(s): Shiokawa, D., Shika, Y., Araki, S., Sunaga, S., Mizuta, R., Kitamura, D. and Tanuma, S.
  • Journal Title: Cell Death Differ 14 Pages: 992-1000
• [Journal Article] Hematopoietic lineage cell specific protein 1(HS1)is a functionally important signaling molecule in platelet activation. (2007)
  • Author(s): Bryan N. Kahner
  • Journal Title: Blood 110 Pages: 2449-2456
  • Peer Reviewed
• [Journal Article] Stage-specific expression of DNase gamma during B-cell development and its role in B-cell receptor-mediated apoptosis in WEHI-231 cells. (2007)
  • Author(s): Daisuke Shiokawa
  • Journal Title: Cell Death Differ. 14 Pages: 992-1000
  • Peer Reviewed
• [Presentation] ネクローシスDNA断片化酵素DNaseγの生理的機能 (2008)
  • Author(s): 水田龍信、鈴木浩平、荏原翔太、古川祐樹、北村大介
  • Organizer: 第31回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] PKCη directs induction of IRF-4 expression and Ig κ gene rearrangement in pre-BCR signaling pathway. (2008)
  • Author(s): Akihisa Oda
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-01
• [Presentation] pre-BCRシグナル伝達経路においてIRF-4の発現とL鎖遺伝子再構成はPKCη により誘導される (2008)
  • Author(s): 小田朗永、小野友宏、山本睦美、後飯塚僚、北村大介
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] B細胞初期分化に重要なpre-BCRの発現制御におけるLAPTM5 の役割 (2008)
  • Author(s): 河野洋平、大内田理佳、王継揚、山本睦美、北村大介、烏山一
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] 抗原受容体シグナル伝達における新規膜タンパク質CMTM7の役割 (2008)
  • Author(s): 宮崎敦子、北村大介
  • Organizer: 第38 回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] IL-4 promotes memory-like B cell generation in vitro (2008)
  • Author(s): 野嶋卓也、白鳥行大、北村大介
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] Meis1欠損マウスにおける胸腺形成異常 (2008)
  • Author(s): 平山雄啓、後飯塚僚、飛騨野真也、河合康洋、丸太博之、北村大介、中村卓郎
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] SLP-76 is required for the high affinity IgE receptor- and cytokine receptor-induced activation of basophils (2008)
  • Author(s): 飛騨野真也、有木玲菜、北村大介、後飯塚僚
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 京都
• [Presentation] DNaseγはネクローシスDNA断片化酵素である (2007)
  • Author(s): 水田龍信、北村大介
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] B細胞抗原受容体のエンドサイトーシスに関与するCMTM3/BNAS2 の機能解析 (2007)
  • Author(s): 與五沢里美、引場樹里、北村大介
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Molecular mechanism of BASH-mediated preBCR down-regulation (2007)
  • Author(s): 河野洋平、山本睦美、北村大介、烏山一
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] A Gads-binding RXXK motif determines the differential membrane targeting and functions of SLP-76 and MIST in FcεRI signaling in mast cells (2007)
  • Author(s): 廣田朋子、飛騨野真也、河合康洋、北村大介、後飯塚僚
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Toward the establishment of germinal center-like B cell culture system (2007)
  • Author(s): 野嶋卓也、白鳥行大、北村大介
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Toward the establishment of germinal center-like B cell culture system. (2007)
  • Author(s): 野嶋 卓也
  • Organizer: 第37回日本免疫学会総会・学術集会
  • Place of Presentation: 東京
• [Book] Self-nonself recognition through B-cell antigen receptor. In : Kitamura, D. eds. How the Immune System Recognizes Self and Nonself : Immunoreceptors and Their Signaling (2007)
  • Author(s): Kitamura, D.
  • Publisher: Springer
• [Book] 「抗原受容体シグナル伝達とB細胞分化・活性化」免疫応答と免疫病態の統合的分子理解 (2007)
  • Author(s): 北村大介
  • Publisher: 南山堂
• [Book] How the Immune System Recognizes Self and Nonself: Immunoreceptors and Their Signaling (2007)
  • Author(s): Daisuke Kitamura
  • Total Pages: 251
  • Publisher: Springer