Analysis of the mechanism of mature B cell differentiation controlled by survival signals from BCR and BAFF-R

• Project/Area Number: 23590575
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Kyoto University (2012-2013); The Institute of Physical and Chemical Research (2011)
• Principal Investigator: SASAKI YOSHITERU 京都大学, 医学(系)研究科(研究院), 准教授 (80323004)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: B細胞 / シグナル伝達 / 遺伝子改変マウス / NF-kB

Research Abstract

Signals from BCR and BAFF-R control the differentiation of mature B cells as well as their survival. In this research I investigated the roles of signals from BCR and BAFF-R in the differentiation of mature B cells and found that Akt, one of the target molecule of PI3 kinase, which transmits the survival signal from BCR plays an important role in B1 cell development and that the main function of the canonical NF-kappaB pathway in the generation of mature B2 and MZ B cells is the control of the strength of BAFF-R mediated alternative NF-kappaB signaling. I also examined the function of a novel ubiquitin ligase complex, LUBAC in B cells and discovered that LUBAC plays important roles in the development of B1 cells and the antibody responses and is required for the activation of the canonical NF-kappaB pathway by CD40 and TACI but not by BCR.

Research Products

• [Journal Article] Defective immune reponses in mice lacking LUBAC-mediated linear ubiquitination in B cells (2013)
  • Author(s): Sasaki, Y., Sano, S., Nakahara, M., Murata, S., Kometani, K., Aiba, Y., Sakamoto, S., Watanabe, Y., Tanaka, K., Kurosaki, T. and Iwai, K.
  • Journal Title: EMBO J . Volume: 32 Pages: 2463-2463
  • Peer Reviewed
• [Journal Article] Defective immune reponses in mice lacking LUBAC-mediated linear ubiquitination in B cells. (2013)
  • Author(s): Sasaki, Y., Sano, S., Nakahara, M., Murata, S., Kometani, K., Aiba, Y., Sakamoto, S., Watanabe, Y., Tanaka, K., Kurosaki, T. and Iwai, K.
  • Journal Title: EMBO Journal Volume: 32 Pages: 2463-2476
  • Peer Reviewed
• [Presentation] Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells (2014)
  • Author(s): 佐々木義輝
  • Organizer: Keystone Symposia, The NF-κB System in Health and Disease
  • Place of Presentation: Keystone Colorado USA (Keystone Resort)
  • Year and Date: 2014-02-26
• [Presentation] Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells (2014)
  • Author(s): 佐々木義輝
  • Organizer: Keystone Symposia The NF-kB System in Health and Disease
  • Place of Presentation: Keystone Colorado USA
• [Presentation] B細胞の発生・機能における直鎖状ポリユビキチン鎖の機能解析 (2013)
  • Author(s): 佐々木義輝
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 神奈川県横浜市(パシフィコ横浜)
  • Year and Date: 2013-09-12
• [Presentation] Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells (2013)
  • Author(s): 佐々木義輝
  • Organizer: 第42回 日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
• [Presentation] B細胞の発生・機能における直鎖状ポリユビキチン鎖の機能解析 (2013)
  • Author(s): 佐々木義輝
  • Organizer: 第86回 生化学会大会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Defective immune responses in mice lacking LUBAC-mediated linear ubiquitination in B cells (2012)
  • Author(s): 佐々木義輝
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉県千葉市(幕張メッセ)
  • Year and Date: 2012-12-12
• [Presentation] LUBAC controls B lymphocyte development and function (2012)
  • Author(s): 佐々木義輝,岩井一宏
  • Organizer: IEIIS2012
  • Place of Presentation: 東京都(学術総合センター)
  • Year and Date: 2012-10-25
• [Presentation] LUBAC controls B lymphocyte development and function (2012)
  • Author(s): Yoshiteru Sasaki, Kazuhiro Iwai
  • Organizer: IEIIS2012
  • Place of Presentation: Tokyo
• [Presentation] Canonical NF-κB pathway controls the strength of BAFF-R signaling through the induction of p100NF-κB2 (2011)
  • Author(s): 佐々木義輝
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: 千葉県千葉市(幕張メッセ)
  • Year and Date: 2011-11-28
• [Presentation] Canonical NF-kB pathway controls the strength of BAFF-R signaling through the induction of p100NF-kB2
  • Author(s): 佐々木 義輝
  • Organizer: 第40回 日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
• [Remarks]
  • URL: http://www.mcp.med.kyoto-u.ac.jp