Molecular mechanisms underlying the development and function of follicular helper T cells

• Project/Area Number: 25293115
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Ise Wataru 大阪大学, 免疫学フロンティア研究センター, 特任准教授 (70323483)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: ヘルパーT細胞 / 抗体産生 / 転写因子

Outline of Final Research Achievements

In order to clarify the molecular mechanisms of development and maintenance of follicular helper T cells (TFH cells), the followings have been demonstrated or shown in three years.
1) In vitro culture to induce TFH-like cells with high levels of Bcl6 was established. 2) TFH cells were able to survived as long-term memory T cells. Antigen-specific memory B cells serves as antigen-presenting cells during secondary activation of memory TFH cells. 3) The conditional knock-out/GFP-reporter mice of the transcription factor BATF were generated. TFH cells express high levels of BATF. 4) Inducible deletion of BATF after germinal center has been established elicited the collapse of germinal center.

Research Products

• [Journal Article] Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells. (2014)
  • Author(s): Ise W, Inoue T, McLachlan JB, Kometani K, Kubo M, Okada T, Kurosaki T
  • Journal Title: Proc Natl Acad Sci U S A Volume: 111 Issue: 32 Pages: 11792-11797
  • DOI: 10.1073/pnas.1404671111
  • Peer Reviewed / Open Access
• [Presentation] Regulation of germinal center response by the transcription factor BATF (2014)
  • Author(s): Wataru Ise and Tomohiro Kurosaki
  • Organizer: 日本免疫学会
  • Place of Presentation: 国立京都国際会館（京都府京都市左京区）
  • Year and Date: 2014-12-11
• [Presentation] Regulation of germinal center response by BATF (2014)
  • Author(s): Wataru Ise and Tomohiro Kurosaki
  • Organizer: 免疫記憶ワクチン国際研究会
  • Place of Presentation: La Jolla, California, USA
  • Year and Date: 2014-08-25 – 2014-08-26
• [Presentation] Memory antibody response is regulated by antigen-specific CXCR5+ memory CD4+ T cells
  • Author(s): Wataru Ise and Tomohiro Kurosaki
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉