Molecular analyses of B-cell memory development through synthetic immunology

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659225
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Tokyo University of Science
• Principal Investigator: KITAMURA Daisuke 東京理科大学, 生命医科学研究所, 教授 (70204914)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 免疫応答 / 免疫学的記憶 / 胚中心 / 細胞分化 / B細胞

Research Abstract

Upon immunization, B cells proliferate to form germinal centers (GC) in the lymphoid organs and differentiate into either long-lived plasma (LP) or memory B (Bmem) cells. Mechanisms for Bmem cell development remain poorly understood, partly due to the lack of an in vitro model system. Recently, we have established a culture system in which naïve B cells undergo massive expansion and isotype switching, and generate GC-like B cells termed iGB cells. The iGB cells after primary IL-4 culture differentiate into functional Bmem-like (iMB) cells in mice, whereas those after the secondary IL-21 culture differentiate into LP but not iMB cells. Thus, this system will facilitate dissection of GC-B cell differentiation programs. In conjunction with knock-out mice, we demonstrated that transcription factor Bach2 and others are required not only for Bmem development. Systematic reconstitution of these factors in iGB cells will allow us to understand the mechanism for Bmem development.

Research Products

• [Journal Article] A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro (2014)
  • Author(s): Moutai, T., Yamana, H., Nojima, T., Kitamura, D.
  • Journal Title: PLoS One Volume: 9 Pages: e92732
  • DOI: 10.1371/journal.pone.0092732
  • Peer Reviewed
• [Journal Article] DNaseγIs the Effector Endonuclease for Internucleosomal DNA Fragmentation in Necrosis (2013)
  • Author(s): Mizuta R, Araki S, Furukawa M, Furukawa Y, Ebara S, Shiokawa D, Hayashi K, Tanuma S, Kitamura D.
  • Journal Title: PLoS One Volume: 8 Pages: e80223
  • DOI: 10.1371/journal.pone.0080223
  • Peer Reviewed
• [Journal Article] Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis (2013)
  • Author(s): Caganova, M., Carrisi, C., Varano, G., Mainoldi, F., Zanardi, F., Germain, P.L., George, L., Alberghini, F., Ferrarini, L., Talukder, A.K., Ponzoni, M., Testa, G., Nojima, T., Doglioni, C., Kitamura, D., Toellner, K.M., Su, I.H., Casola, S.
  • Journal Title: J. Clin. Invest Volume: 123 Pages: 5009-5022
  • DOI: 10.1172/JCI70626
  • Peer Reviewed
• [Journal Article] A novel mechanism for the autonomous termination of pre-B cell receptor expression via induction of lysosomal-associated protein transmembrane 5 (2012)
  • Author(s): Kawano, Y., Ouchida, R., Wang, J.Y., Yoshikawa, S., Yamamoto, M., Kitamura, D., Karasuyama, H.
  • Journal Title: Mol. Cell. Biol Volume: 32 Pages: 4462-4471
  • DOI: 10.1128/MCB.00531-12
  • Peer Reviewed
• [Journal Article] SLP-76 is required for high-affinity IgE receptor- and IL-3 receptor-mediated activation of basophils (2012)
  • Author(s): Hidano, S., Kitamura, D., Kumar, L., Geha, R.S., Goitsuka, R.
  • Journal Title: Int. Immunol Volume: 24 Pages: 719-727
  • DOI: 10.1093/intimm/dxs072
  • Peer Reviewed
• [Journal Article] Syk-dependent signaling pathways in neutrophils and macrophages are indispensable in the pathogenesis of anti-collagen antibody-induced arthritis (2012)
  • Author(s): Ozaki, N., Suzuki, S., Ishida, M., Harada, Y., Tanaka, K., Sato, Y., Kono, T., Kubo, M., Kitamura, D., Encinas, J., Hara, H. Yoshida, H.
  • Journal Title: Int. Immunol Volume: 24 Pages: 539-550
  • DOI: 10.1093/intimm/dxs078
  • Peer Reviewed
• [Journal Article] E2A and CBP/p300 act in synergy to promote chromatin accessibility of the immunoglobulinκlocus (2012)
  • Author(s): Sakamoto, S., Wakae, K., Anzai, Y., Murai, K., Tamaki, N., Miyazaki, M., Miyazaki, K., Romanow, W. J., Ikawa, T., Kitamura, D., Yanagihara, I., Minato, N., Murre, C. Agata, Y.
  • Journal Title: J. Immunol Volume: 188 Pages: 5547-5560
  • DOI: 10.4049/jimmunol.1002346
  • Peer Reviewed
• [Presentation] Molecular mechanisms for memory B-cell development and function (2013)
  • Author(s): Daisuke Kitamura, Kei Haniuda, Saori Fukao, Mika Inada, Shu Horiuchi, Shogo Takatsuka, Tatsuya Moutai, Takuya Nojima
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
  • Year and Date: 20130822-27
• [Presentation] Molecular requirements for memory B-cell development (2013)
  • Author(s): Daisuke Kitamura
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ
  • Year and Date: 2013-12-13
• [Presentation] Regulatory mechanisms for memory B cell development and function (2013)
  • Author(s): Daisuke Kitamura
  • Organizer: The 1st Symposium of International Immunological Memory and Vaccine Forum."Immunological Memory and Vaccine"
  • Place of Presentation: 東京
  • Year and Date: 2013-01-29
• [Presentation] A new cancer therapy using induced germinal center B cells (2012)
  • Author(s): Daisuke Kitamura
  • Organizer: The 3rd Workshop of Synthetic Immunology
  • Place of Presentation: 京都
  • Year and Date: 2012-05-18
• [Book] 岩波生物学辞典第5版 (2013)
  • Author(s): 北村大介、他多数
  • Total Pages: 2192
  • Publisher: 岩波書店