Molecular mechanisms of memory B cell differentiation in germinal centers

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390121
• 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 千葉大学, 医学(系)研究科(研究院), 教授 (20134364)
• Co-Investigator(Kenkyū-buntansha): 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)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 免疫記憶 / Ｂリンパ球 / 胚中心 / サイトカイン / 抗体産生細胞 / IgE抗体

Research Abstract

To elucidate a role of IL-21 or Bcl6 in differentiation of high affinity IgG producing memory B cells and long-lived plasma cells in germinal centers, we used IL-21-deficient or Bcl6-deficient mice. Using these mice, we demonstrated that IL-21 is essential to differentiation of high affinity IgG producing long-lived plasma cells, and that IL-21 or Bcl6 represses the Ig class switch recombination to IgE and augments the differentiation of high affinity IgG producing memory B cells and long-lived plasma cells.

Research Products

• [Journal Article] Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells (2014)
  • Author(s): Ikari J, Inamine A, Yamamoto T, Watanabe-Takano H, Yoshida N, Fujimura L, Taniguchi T, Sakamoto A, Hatano M, Tatsumi K, Tokuhisa T, and Arima M
  • Journal Title: Allergy Volume: 69 Pages: 223-230
  • DOI: 10.1111/all.12328
  • Peer Reviewed
• [Journal Article] Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis (2013)
  • Author(s): Takahashi W, Watanabe E, Fujimura L, Watanabe-Takano H, Yoshidome H, Swanson PE, Tokuhisa T, Oda S, and Hatano M
  • Journal Title: Crit. Care Volume: 17 Pages: R160
  • Peer Reviewed
• [Journal Article] Lack of both α2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production (2013)
  • Author(s): Okada K, Ueshima S, Kawao N, Yano M, Tamura Y, Tanaka M, Sakamoto A, Hatano M, Arima M, Miyata S, Nagai N, Tokuhisa T, and Matsuo O
  • Journal Title: Life Sci Volume: 93 Pages: 89-95
  • DOI: 10.1016/j.lfs.2013.05.023
  • Peer Reviewed
• [Journal Article] Leukotriene C4 aggravates bleomycin-induced pulmonary fibrosis in mice (2013)
  • Author(s): Hirata H, Arima M, Fukushima Y, Sugiyama K, Tokuhisa T, and Fukuda T
  • Journal Title: Respirology Volume: 18 Pages: 674-681
  • DOI: 10.1111/resp.12072
  • Peer Reviewed
• [Journal Article] ADAR1 protein induces adenosine-targeted DNA mutations in senescent Bcl6 gene-deficient cells (2013)
  • Author(s): Tsuruoka N, Arima M, Yoshida N, Okada S, Sakamoto A, Hatano M, Satake H, Arguni E, Wang Ji-Y, Yang J-H, Nishikura K, Sekiya S, Shozu M, and Tokuhisa T
  • Journal Title: J. Biol. Chem Volume: 288 Pages: 826-836
  • DOI: 10.1074/jbc.M112.365718
  • Peer Reviewed
• [Journal Article] Generation of tissue-specific H-2K(d) transgenic mice for the study of K(d)-restricted malaria epitope-specific CD8(+) T-cell responses in vivo (2013)
  • Author(s): Huang J, Li X, Kohno K, Hatano M, Tokuhisa T, Murray PJ, Brocker T, and Tsuji M
  • Journal Title: J. Immunol. Methods Volume: 387 Pages: 254-261
  • DOI: 10.1016/j.jim.2012.10.019
  • Peer Reviewed
• [Journal Article] Critical role of the IgM Fc receptor in IgM homeostasis, B cell survival, and humoral immune responses (2012)
  • Author(s): Ouchida R, Mori H, Hase K, Takatsu H, Kurosaki T, Tokuhisa T, Ohno H, and Wang Ji-Yang
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 109 Pages: 2699-2706
  • DOI: 10.1073/pnas.1210706109
  • Peer Reviewed
• [Journal Article] CD40 amplifies Fas-mediated apoptosis : a mechanism contributing to emphysema (2012)
  • Author(s): Shigeta A, Tada Y, Wang JY, Ishizaki S, Tsuyusaki J, Yamauchi K, Kasahara Y, Iesato K, Tanabe N, Takiguchi Y, Sakamoto A, Tokuhisa T, Shibuya K, Hiroshima K, West J, and Tatsumi K
  • Journal Title: Am. J. Physiol. Lung Cell Mol. Physiol Volume: 303 Pages: 141-151
  • DOI: 10.1152/ajplung.00337.2011
  • Peer Reviewed
• [Journal Article] BAZF, a novel component of cullin3-based E3 ligase complex, mediates VEGFR and Notch cross-signalling in angiogenesis (2012)
  • Author(s): Ohnuki H, Inoue H, Takemori N, Nakayama H, Sakaue T, Fukuda S, Miwa D, Nishiwaki E, Hatano M, Tokuhisa T, Endo Y, Nose M, and Higashiyama S
  • Journal Title: Blood Volume: 119 Pages: 2688-2698
  • DOI: 10.1182/blood-2011-03-345306
  • Peer Reviewed
• [Journal Article] Bcl6 in pulmonary epithelium coordinately controls the expression of the CC-type chemokine genes and attenuates allergic airway inflammation (2011)
  • Author(s): Seto T, Yoshitake M, Ogasawara T, Ikari J, Sakamoto A, Hatano M, Hirata H, Fukuda T, Kuriyama T, Tatsumi K, Tokuhisa T, and Arima M
  • Journal Title: Clin. Exp. Allergy Volume: 41 Pages: 1568-1578
  • DOI: 10.1111/j.1365-2222.2011.03836.x
  • Peer Reviewed
• [Journal Article] Over-expression of the LTC(4) synthase gene in mice reproduces human aspirin-induced asthma (2011)
  • Author(s): Hirata H, Arima M, Fukushima Y, Honda K, Sugiyama K, Tokuhisa T, and Fukuda T
  • Journal Title: Clin. Exp. Allergy Volume: 41 Pages: 1133-1142
  • DOI: 10.1111/j.1365-2222.2011.03720.x
  • 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, and Uno H
  • Journal Title: Cytokine Volume: 54 Pages: 79-84
  • DOI: 10.1016/j.cyto.2010.12.001
  • Peer Reviewed
• [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, and Tokuhisa T
  • Journal Title: J. Immunol Volume: 186 Pages: 2800-2808
  • DOI: 10.4049/jimmunol.1003401
  • 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, and Tokuhisa T
  • Journal Title: J. Immunol Volume: 186 Pages: 255-263
  • DOI: 10.4049/jimmunol.0903714
  • Peer Reviewed
• [Presentation] 免疫記憶細胞の形成と維持 (2014)
  • Author(s): 徳久剛史
  • Organizer: 東京免疫フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2014-02-24
• [Presentation] IgE 抗体産生機構と制御法の開発 (2013)
  • Author(s): 徳久剛史, 有馬雅史
  • Organizer: 第25回日本アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 2013-05-12
• [Presentation] Development of High Affinity IgE B Cells (2013)
  • Author(s): Tokuhisa T
  • Organizer: Chiba and Auckland University Immunology Forum
  • Place of Presentation: New Zealand
  • Year and Date: 2013-02-23
• [Presentation] 免疫記憶細胞の形成と維持 (2012)
  • Author(s): 徳久剛史
  • Organizer: 第40回日本臨床免疫学会
  • Place of Presentation: 東京
  • Year and Date: 2012-09-29
• [Presentation] 若き臨床研究者たちへ (2012)
  • Author(s): 徳久剛史
  • Organizer: 第51回日本鼻科学会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2012-09-28
• [Presentation] 免疫記憶と慢性アレルギー (2012)
  • Author(s): 徳久剛史
  • Organizer: 第6回日本アミノ酸学会
  • Place of Presentation: 松戸市
  • Year and Date: 2012-09-28
• [Presentation] 老化すると免疫記憶にもボケがでるか (2011)
  • Author(s): 徳久剛史
  • Organizer: 第11回日本抗加齢医学会「加齢と免疫」シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2011-05-28
• [Remarks] 分化制御学教室のホームページ
  • URL: http://www.m.chiba-u.ac.jp/class/devgen