Survival mechanism of memory B cells

• Project/Area Number: 20390139
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Immunology
• Research Institution: Chiba University
• Principal Investigator: TOKUHISA Takeshi Chiba University, 大学院・医学研究院, 教授 (20134364)
• Co-Investigator(Kenkyū-buntansha): HATANO Masahiko 千葉大学, 大学院・医学研究院, 教授 (20208523) ; ARIMA Masafumi 千葉大学, 大学院・医学研究院, 講師 (00202763) ; SAKAMOTO Akemi 千葉大学, 大学院・医学研究院, 助教 (90359597) ; FUJIMURA Riza 千葉大学, バイオメディカル研究センター, 助教 (30376363)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000); Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2009: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 免疫記憶 / Bリンパ球 / 胚中心 / サイトカイン / Niche / CXCR4 / IL-21 / Long-lived Plasma細胞

Research Abstract

To elucidate differentiation mechanisms of memory B cells and long-lived plasma cells, we established the culture system to generate germinal center B cells. Using the system, we demonstrated that Bcl6 represses CD63 which recruits CXCR4 to late endosome to express CXCR4 on centroblasts and that the stimulation of plasmablasts with IL-21 generates long-lived plasma cells.

Research Products

• [Journal Article] CXCR4 expression on activated B cells is down-regulated by CD63 and IL-21. (2011)
  • Author(s): Yoshida N, Kitayama D, Arima M, Sakamoto A, Inamine A, Takano H, Hatano M, Koike T, Tokuhisa T
  • Journal Title: J.Immunol. 186 Pages: 2800-2808
  • Peer Reviewed
• [Journal Article] Bcl6 is required for the development of mouse CD4^+ and CD8α^+ dendritic cells. (2011)
  • Author(s): Ohtsuka H, Sakamoto A, Pan J, Inage S, Horigome S, Ichii H, Arima M, Hatano M, Okada S, Tokuhisa T
  • Journal Title: J.Immunol. 186 Pages: 255-263
  • Peer Reviewed
• [Journal Article] Outcome prediction in sepsis combined use of genetic polymorphisms- A study in Japanese population. (2011)
  • Author(s): Shimada T, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Watanabe E, Abe R, Nakada TA, Tateishi Y, Otani S, Hirasawa H, Tokuhisa T, Uno H
  • Journal Title: Cytokine 54 Pages: 79-84
  • Peer Reviewed
• [Journal Article] CXCR4 expression on activated B cells is down-regulated by CD63 and lL-21. (2011)
  • Author(s): Yoshida, N., etal.
  • Journal Title: J.Immunol. Volume: 186 Pages: 2800-2808
  • Peer Reviewed
• [Journal Article] Augmented antibody response with premature germinal center regression in CD40L-transgenic mice. (2010)
  • Author(s): Kishi Y, Aiba Y, Higuchi T, Furukawa K, Tokuhisa T, Takemori T, Tsubata T
  • Journal Title: J.Immunol. 185 Pages: 211-219
  • Peer Reviewed
• [Journal Article] The Blimp1-Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis. (2010)
  • Author(s): Miyauchi Y, Ninomiya K, Miyamoto H, Sakamoto A, Iwasaki R, Hoshi H, Miyamoto K, Hao W, Yoshida S, Morioka H, Chiba K, Kato S, Tokuhisa T, Saitou M, Toyama Y, Suda T, Miyamoto T
  • Journal Title: J.Exp.Med. 207 Pages: 751-762
  • Peer Reviewed
• [Journal Article] The proto-oncogene BCL6 promotes survival of olfactory sensory neurons. Dev. (2010)
  • Author(s): Otaki JM, Hatano M, Matayoshi R, Tokuhisa T, Yamamoto H
  • Journal Title: Neurobiol. 70 Pages: 424-435
  • Peer Reviewed
• [Journal Article] The Blimpl-Bc16 axis is critical to regulate osteoclast differentiation and bone homeostasis. (2010)
  • Author(s): Miyauchi, Y., etal.
  • Journal Title: J.Exp.Med. Volume: 207 Pages: 751-762
  • Peer Reviewed
• [Journal Article] Augmented antibody response with premature germinal center regressi on in CD40L-transgenic mice. (2010)
  • Author(s): Kishi, Y., etal.
  • Journal Title: J.Immunol. Volume: 185 Pages: 211-219
  • Peer Reviewed
• [Journal Article] TBP (TATA-binding protein)-like protein (TLP) is engaged in etoposide-induced apoptosis through transcriptional activation of humanTAp63 Gene. (2009)
  • Author(s): Suenaga Y, Ozaki T, Tanaka Y, Bu Y, Kamijo T, Tokuhisa T, Nakagawara A, Tamura TA
  • Journal Title: J.Biol.Chem. 284 Pages: 35433-35440
  • Peer Reviewed
• [Journal Article] A kelch family protein Nd1-L functions as a metastasis suppressor in cancer cells via Rho family proteins mediated mechanism. (2009)
  • Author(s): Ohta Y, Fujimura L, Nishio S, Arima M, Sakamoto A, Shimada H, Ochiai T, Tokuhisa T, Hatano M
  • Journal Title: Int.J.Oncology 36 Pages: 427-434
  • Peer Reviewed
• [Journal Article] Prickle promotes neurite outgrowth via the Dishevelled dependent pathway in C1300 cells. (2009)
  • Author(s): Fujimura L, Takano H, Sato Y, Tokuhisa T, Hatano M
  • Journal Title: Neuroscience Letters 467 Pages: 6-10
  • Peer Reviewed
• [Journal Article] Clinical application of cytokine-related gene polymorphism analysis using a newly developed DNA chip in critically ill patients. (2009)
  • Author(s): Otani S, Oda S, Sadahiro T, Nakamura M, Watanabe E, Abe R, Tokuhisa T, Hirasawa H
  • Journal Title: Clin.Biochem. 42 Pages: 1387-1393
  • Peer Reviewed
• [Journal Article] TBP(TATA-binding protein)-like protein(TLP)is engaged in etoposide-induced apoptosis through transcriptional activation of humanTAp63 Gene. (2009)
  • Author(s): Suenaga, Y., et al.
  • Journal Title: J.Biol.Chem. 284 Pages: 35433-35440
  • Peer Reviewed
• [Journal Article] A kelch family protein Nd1-L functions as a metastasis suppress or in cancer cells via Rho family proteins mediated mechanism. (2009)
  • Author(s): Ohta, Y., et al.
  • Journal Title: Int.J.Oncology 36 Pages: 427-434
  • Peer Reviewed
• [Journal Article] Prickle promotes neurite outgrowth via the Dishevelled dependent pathway in C1300 cells. (2009)
  • Author(s): Fujimura, L., et al.
  • Journal Title: Neuroscinece Letters 467 Pages: 6-10
  • Peer Reviewed
• [Journal Article] IL-23 and Th17 cells enhance Th2 cell-mediated eosinophilic airway inflammation in mice. (2008)
  • Author(s): Wakashin H, Hirose K, Maezawa Y, Kagami, S-I, Suto A, Watanabe N, Saito Y, Hatano M, Tokuhisa T, Iwakura Y, Puccetti P, Iwamoto I, Nakajima H
  • Journal Title: Am.J.Resp.Crit Care Med. 178 Pages: 1023-1032
  • Peer Reviewed
• [Journal Article] Effects of Th2 pulmonary inflammation in mice with bleomycin-induced pulmonary fibrosis. (2008)
  • Author(s): Hirata H, Arima M, Fukushima Y, Ishii Y, Tokuhisa T, Fukuda T
  • Journal Title: Respirology 13 Pages: 788-798
  • Peer Reviewed
• [Journal Article] Role of the transcriptional repressor BCL6 in allergic response and inflammation. (2008)
  • Author(s): Arima M, Fukuda T, Tokuhisa T
  • Journal Title: WAO Journal Pages: 115-122
  • Peer Reviewed
• [Journal Article] Genetic analysis reveals an intrinsic property of the germinal center B cells to generate A : T mutations. (2008)
  • Author(s): Ouchida R, Ukai A, Mori H, Kawamura K, Dolle MET, Tagawa M, Sakamoto A, Tokuhisa T, Yokosuka T, Saito T, Yokoi M, Hanaoka F, Vijg J, Wang Ji-Y
  • Journal Title: DNA Repair 7 Pages: 1392-1398
  • Peer Reviewed
• [Journal Article] A lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3ζ degradation. (2008)
  • Author(s): Ouchida R, Yamasaki S, Hikida M, Masuda K, Kawamura K, Wada A, Mochizuki S, Tagawa, M, Sakamoto A, Hatano M, Tokuhisa T, Koseki H, Saito T, Kurosaki T, Wang Ji-Y
  • Journal Title: Immunity 29 Pages: 33-43
  • Peer Reviewed
• [Journal Article] A distinct role for IL-4 and IL-21 in their collaboration on proliferation and differentiation of activated B cells. (2008)
  • Author(s): Saito T, Kitayama D, Sakamoto A, Tsuruoka N, Arima M, Hatano M, Miyazaki M, Tokuhisa T
  • Journal Title: Immunobiol. 213 Pages: 545-555
  • Peer Reviewed
• [Journal Article] A role for Bcl6 in sequential class switch recombination to IgE in B cells stimulated with IL-4 and IL-21. (2008)
  • Author(s): Kitayama D, Sakamoto A, Arima M, Hatano M, Miyazaki M, Tokuhisa T
  • Journal Title: Mol.Immunol. 45 Pages: 1337-1345
  • Peer Reviewed
• [Journal Article] A role for Bcl6 in sequential class switch recombination to IgE in B cells stimulated with IL-4 and IL-2I. (2008)
  • Author(s): Kitayama, D., et al.
  • Journal Title: Mol. Immunol 45 Pages: 1337-1345
  • Peer Reviewed
• [Journal Article] A lysosomal protein negatively regulates surface Tcellantigen receptor expression by promoting CD3 ζ degradation. (2008)
  • Author(s): Ouchida, R., et al.
  • Journal Title: Immunity 29 Pages: 33-43
  • Peer Reviewed
• [Journal Article] IL-23 and Th17 Cells Enhance Th2 Cell-mediated Eos inophilic Airway Inflammation in Mice. (2008)
  • Author(s): Wakashin, H., et al.
  • Journal Title: Am. J. Resp. Crit. Care Med. 178 Pages: 1023-1032
  • Peer Reviewed
• [Presentation] Role for Bcl6 in Differentiation of High Affinity IgE B Cells (2010)
  • Author(s): 徳久剛史
  • Organizer: 5th G-COE symposium.
  • Place of Presentation: Tokyo
  • Year and Date: 2010-12-04
• [Presentation] 高親和性IgE抗体産生細胞の分化とヘルパーT細胞の多様性 (2010)
  • Author(s): 徳久剛史
  • Organizer: 第60回日本アレルギー学会
  • Place of Presentation: 東京(特別講演)
  • Year and Date: 2010-11-26
• [Presentation] 高親和性IgE抗体産生細胞の分化とヘルパーT細胞の多様性 (2010)
  • Author(s): 徳久剛史、有馬雅史
  • Organizer: 第60回日本アレルギー学会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-26
• [Presentation] アレルギーは治せるか (2010)
  • Author(s): 徳久剛史
  • Organizer: 千葉大経済人クラブ
  • Place of Presentation: 浦安
  • Year and Date: 2010-10-04
• [Presentation] 研究指導者に望まれる資質 (2010)
  • Author(s): 徳久剛史
  • Organizer: G-COEリトリート
  • Place of Presentation: 千葉
  • Year and Date: 2010-09-05
• [Presentation] Roles for Bcl6 in differentiation of germinal center B cells (2010)
  • Author(s): 徳久剛史
  • Organizer: 4th G-COE symposium.
  • Place of Presentation: Chiba
  • Year and Date: 2010-08-20
• [Presentation] 部局の活性化にむけて (2010)
  • Author(s): 徳久剛史
  • Organizer: 創立60周年記念大学改革シンポジウム
  • Place of Presentation: 千葉
  • Year and Date: 2010-01-25
• [Presentation] Role for Bcl6 in development and maintenance of germinal center B cells (2009)
  • Author(s): 徳久剛史
  • Organizer: LAH 50th Symposium
  • Place of Presentation: Stanford, USA
  • Year and Date: 2009-11-06
• [Presentation] Role for Bc16 in development and maintenance of germinal center B cells (2009)
  • Author(s): Tokuhisa, T.
  • Organizer: LAH 50th Memorial Symposium
  • Place of Presentation: 米国カリフォルニア州スタンフォード市
  • Year and Date: 2009-11-06
• [Presentation] Role for Bcl6 in development and maintenance of germinal center B cells (2009)
  • Author(s): 徳久剛史
  • Organizer: RISP2009 Lecture
  • Place of Presentation: Yokohama
  • Year and Date: 2009-07-06
• [Presentation] 抗体の威力 (2009)
  • Author(s): 徳久剛史
  • Organizer: 免疫ふしぎ未来2009免疫シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-05-02
• [Presentation] IgE抗体の産生機 (2009)
  • Author(s): 徳久剛史
  • Organizer: 第17回関東アレルギークラブ
  • Place of Presentation: 東京(特別講演)
  • Year and Date: 2009-03-07
• [Presentation] IgE抗体の産生機構 (2009)
  • Author(s): 徳久剛史
  • Organizer: 第17回関東アレルギークラブ
  • Place of Presentation: 東京都
  • Year and Date: 2009-03-07
• [Presentation] Possible roles for Bcl6 in differentiation of Germinal Center B cells (2009)
  • Author(s): 徳久剛史
  • Organizer: 1st G-COE symposium.
  • Place of Presentation: Tokyo
  • Year and Date: 2009-01-06
• [Presentation] Self-Tolerance in Germinal Center B cells (2008)
  • Author(s): 徳久剛史
  • Organizer: Immunological Self-Recognition and Its Disorders.
  • Place of Presentation: Kyoto
  • Year and Date: 2008-07-03
• [Presentation] 医学部における寄生虫学教育 (2008)
  • Author(s): 徳久剛史
  • Organizer: 第77回日本寄生虫学会シンポジウム
  • Place of Presentation: 長崎
  • Year and Date: 2008-04-03
• [Remarks] ホームページ等
• [Remarks] 分化制御学教室のホームページのURLは、以下の通りである。
  • URL: http://www.m.chiba-u.ac.jp/class/devgen
• [Remarks]
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• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/devgen
• [Remarks]
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