Analysis of regulatory mechanism of early B cell development by Bach transcriptional factors

• Project/Area Number: 21790261
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: MUTO Akihiko Tohoku University, 大学院・医学系研究科, 講師 (80343292)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 細胞医化学 / 転写因子 / 細胞分化 / 遺伝子 / 免疫学 / B細胞 / 造血幹細胞 / Pax5 / Blimp-1

Research Abstract

Lymphocytes develop from hematopoietic stem cells (HSC). The transcription factors that regulate the lymphoid-primed multipotent progenitors (LMPP) development form the multipotent progenitors (MPP) remain to be identified. We found a significant reduction in the frequency and total cell numbers of LMPP but not HSC and MPP in Bach1 and Bach2 double deficient mice (DD mice). The numbers of pro-B cells and pre-B cells of DD mice were also reduced to 30% of WT mice. Bach1 and Bach2 single knockout mice showed no obvious defect in these populations in bone marrow. Therefore, Bach1 and Bach2 are required for the cell fate specification of the lymphocyte lineage including LMPPs and they compensate for each other in this process.

Research Products

• [Journal Article] Heme regulates B-cecll differentiation, antibody class swotch, and heme oxygenase-1 expression in B cells as a ligand of Bach2 (2011)
  • Author(s): Miki Watanabe-Matsui, Akihiko Muto, Toshitaka Matusi, Ari Itoh-Nakadai, Nakajima Osamu, Kazutaka Murayama, Masayuki Yamamoto, Masao Ikeda-Saito, Kazuhiko Igarashi
  • Journal Title: Blood In press
  • Peer Reviewed
• [Journal Article] Heme regulates B cell differentiation, antibody class switch, and heme oxygenase-1 expression in B cell as a ligand of Bach2 (2011)
  • Author(s): Watanabe-Matsui, M., 他
  • Journal Title: Blood Volume: (未定 In press)
  • Peer Reviewed
• [Journal Article] Bach2 represses plasma cell gene regulatory network in B cell to promote antibody class switch (2010)
  • Author(s): Akihiko Muto, Kyoko Ochiai, Yoshitaka Kimura, Ari Itoh-Nakadai, Kyatharin Calame, Dai Ikebe, Satoshi Tashiro, Kazuhiko Igarashi
  • Journal Title: EMBO J. vol.29 Pages: 4048-4061
  • Peer Reviewed
• [Journal Article] Bach1-dependent and-independent regulation of heme oxygenase-1 in leratinocytes (2010)
  • Author(s): S.Okada, A.Muto, E.Ogawa, A.Nakanome, Y.Katoh, S.Ishikawa, S.Aiba, K.Igarashi, R.Okuyama
  • Journal Title: J.Biol.Chem. vol.285 Pages: 23581-23589
  • Peer Reviewed
• [Journal Article] Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch (2010)
  • Author(s): Muto, A., 他
  • Journal Title: EMBO J. Volume: 29 Pages: 4048-4061
  • Peer Reviewed
• [Journal Article] Bach1-dependent and -independent regulation of heme oxygenase-1 in keratinocytes (2010)
  • Author(s): Okada, S., 他
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 23581-23589
  • Peer Reviewed
• [Journal Article] Inhibition of Bach1 ameliorates indomethacin-induced intestinal injyry in mice (2009)
  • Author(s): A.Harusato, Y.naito, T.Takagi, S.Yamada, K.Mizushima, Y.Hirai, R.Horie, K.Inoue, K.Fukumoto, I.Hirata, T.Omatsu, E.Kishimoto, K.Uchiyama, O.Haneda, T.Ishikawa, S.Kokura, H.Ichikawa, A.Muto, K.Igarashi, T.Yoshikawa
  • Journal Title: J.Physiol.Pharmacol. vol.7 Pages: 149-154
  • Peer Reviewed
• [Presentation] The repression of plasma cell differentiation by Bach2 allows activated B cells to execute class switch recombination (2011)
  • Author(s): A.Muto
  • Organizer: ESF-JSPS Frontier Science Conference Series for Young Researchers Cutting Edge Immunology and its Clinical Application
  • Place of Presentation: Hulshort, The Netherlands
  • Year and Date: 2011-03-01
• [Presentation] The repression of plasma cell differentiation by Bach2 allows activated B cells to execute class switch recombination (2011)
  • Author(s): A.Muto
  • Organizer: Tohoku University Global COE for conquest of Signal Transduction Diseases with "Network Medicine" Internal Minisymposium
  • Place of Presentation: 仙台
  • Year and Date: 2011-02-04
• [Presentation] Structure and dynamics of the B cell gene regulatory network that balances antibody class switch and plasma cell differentiation (2010)
  • Author(s): A.Muto, K.Ochiai, Y.Kimura, K.Calame, D.Ikebe, S.Tashiro, K.Igarashi
  • Organizer: 14^<th> International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] Structure and dynamics of the B cell gene regulatory network that balances antibody class switch and plasma cell differentiation (2010)
  • Author(s): 武藤哲彦
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-25
• [Presentation] Bach2 is required for B-1 cell development (2009)
  • Author(s): 武藤哲彦, 五十嵐和彦
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Bach2 is required for B-1 B cell development (2009)
  • Author(s): 武藤哲彦
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Remarks] ホームページ等
  • URL: http://www.biochem.med.tohoku.ac.jp/
• [Remarks]
  • URL: http://www.biochem.med.tohoku.ac.jp/
• [Remarks]
  • URL: http://www.biochem.med.tohoku.ac.jp/