Characterization of an mTORC1-independent B cell differentiation program

• Project/Area Number: 25670236
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Kansai Medical University
• Principal Investigator: MATSUDA Satoshi 関西医科大学, 医学部, 准教授 (00286444)
• Co-Investigator(Renkei-kenkyūsha): OHTANI Masashi 東邦大学, 理学部, 講師 (20383713)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: B細胞分化 / mTORC1シグナル / 腸内細菌 / mTORC1 / IgA

Outline of Final Research Achievements

Mice with a B cell-specific deletion of Raptor (RaptorB-/- mice), an essential component of mammalian target of rapamycin complex 1 (mTORC1), had a developmental arrest at the pro-B cell stage in the bone marrow (BM) and consequently failed to produce detectable levels of IgM and IgG. However, RaptorB-/- mice still produced gut-associated IgA required for controlling gut microbiota. Unexpectedly, RaptorB-/- B cells underwent somatic hyper mutation (SHM) in the gene encoding IgA despite the fact that T follicular helper (TFH) cells were absent. Our findings reveal a gut-associated mTORC1-independent differentiation program of IgA+ B cells, which plays a crucial role in maintaining intestinal homeostasis.

Research Products

• [Journal Article] Pleiotropic roles of mTOR complexes in haemato-lymphopoiesis and leukemogenesis. (2014)
  • Author(s): Hoshii T, Matsuda S, Hirao A.
  • Journal Title: J Biochem. Volume: 156 Issue: 2 Pages: 73-83
  • DOI: 10.1093/jb/mvu037
  • NAID: 40020155036
  • Peer Reviewed
• [Journal Article] Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells. (2013)
  • Author(s): Hoshii T, Kasada A, Hatakeyama T, Ohtani M, Tadokoro Y, Naka K, Ikenoue T, Ikawa T, Kawamoto H, Fehling HJ, Araki K, Yamamura K, Matsuda S, Hirao A
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 10 Pages: 3805-3810
  • DOI: 10.1073/pnas.1320265111
  • Peer Reviewed
• [Presentation] B-lineage specific loss of mTORC1 signal causes selective production of IgA against commensal bacteria. (2014)
  • Author(s): Ohtani, M., Fujii, H., Ohara, O., Koyasu, S., Kubo, M., and Matsuda, S.
  • Organizer: 第４３回日本免疫学会総会・学術集会
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] mTORC1シグナルによるB細胞分化制御 (2014)
  • Author(s): 松田達志、大谷真志、小安重夫，久保允人、平尾敦
  • Organizer: 第24回日本サイトメトリー学会学術集会
  • Place of Presentation: 関西医科大学（大阪府枚方市）
  • Year and Date: 2014-06-28 – 2014-06-29
• [Presentation] mTOR complex 1 is critical for B cell development but not IgA production. (2013)
  • Author(s): Ohatni, M., Fujii, H., Koyasu, S., Kubo, M., and Matsuda, S.
  • Organizer: 第４２回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張（幕張メッセ）
• [Presentation] mTOR complex 1はIgHμ発現を介してB細胞の分化を制御している (2013)
  • Author(s): 大谷 真志、渡辺 貴志、星居 孝之、小安 重夫、小原 收、平尾 敦、久保 允人、松田 達志
  • Organizer: 第３６回日本分子生物学会年会
  • Place of Presentation: 神戸（神戸国際会議場他）
• [Remarks] 関西医科大学附属生命医学研究所生体情報部門ホームページ
  • URL: http://www3.kmu.ac.jp/bioinfo/index.html