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Identification of regulatory B cells in vivo and elucidation of its suppressive mechanism

Research Project

Project/Area Number 24689023
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Immunology
Research InstitutionOsaka University

Principal Investigator

Yoshihiro Baba  大阪大学, 免疫学フロンティア研究センター, 特任准教授 (20415269)

Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
Fiscal Year 2014: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2013: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2012: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywords制御性B細胞 / 炎症 / 自己免疫疾患 / IL-10 / プラズマブラスト / 多発性硬化症 / B細胞 / EAE / 自己免疫性炎症
Outline of Final Research Achievements

B cells can suppress autoimmunity by secreting interleukin-10 (IL-10). Although subpopulations of splenic B lineage cells are reported to express IL- 10 in vitro, the identity of IL-10-producing B cells with regulatory function in vivo remains unknown. By using IL-10 reporter mice, we found that plasmablasts in the draining lymph nodes (dLNs), but not splenic B lineage cells, predominantly expressed IL-10 during experimental autoimmune encephalomyelitis (EAE). These plasmablasts were generated only during EAE inflammation. Mice lacking plasmablasts by genetic ablation of the transcription factor Blimp1 in B lineage cells developed an exacerbated EAE. Hence, plasmablasts in the dLNs serve as IL-10 producers to limit autoimmune inflammation. As with mice, we established that human plasmablasts derived from naive B cells selectively secreted IL-10, reinforcing the importance of plasmablasts as IL-10-producing regulatory cells.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (26 results)

All 2016 2015 2014 2013 2012

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 10 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (6 results)

  • [Journal Article] Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.2016

    • Author(s)
      Ohmi Y, Ise W, Harazono A, Takakura D, Fukuyama H, Baba Y, Narazaki M, Shoda H, Takahashi N, Ohkawa Y, Ji S, Sugiyama F, Fujio K, Kumanogoh A, Yamamoto K, Kawasaki N, Kurosaki T, Takahashi Y, Furukawa K.
    • Journal Title

      Nature Communications

      Volume: in press Issue: 1 Pages: 11205-11205

    • DOI

      10.1038/ncomms11205

    • NAID

      120007135549

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Role of Calcium Signaling in B Cell Activation and Biology.2015

    • Author(s)
      Baba Y & Kurosaki T
    • Journal Title

      Curr. Top. Microbiol. Immunol.

      Volume: 393 Pages: 143-174

    • Related Report
      2015 Annual Research Report
    • Acknowledgement Compliant
  • [Journal Article] Signals controlling the development and activity of regulatory B-lineage cells.2015

    • Author(s)
      Baba, Y., Matsumoto, M., Kurosaki, T.
    • Journal Title

      Int Immunol.

      Volume: 27 Issue: 10 Pages: 487-93

    • DOI

      10.1093/intimm/dxv027

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU.2015

    • Author(s)
      Shanmughapriya S, Rajan S, Hoffman NE, Zhang X, Guo S, Kolesar JE, Hines KJ, Ragheb J, Jog NR, Caricchio R, Baba Y, Zhou Y, Kaufman BA, Cheung JY, Kurosaki T, Gill DL, Madesh M.
    • Journal Title

      Sci Signal.

      Volume: 8 Issue: 366

    • DOI

      10.1126/scisignal.2005673

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation.2014

    • Author(s)
      Mastumoto, M., Baba, A., Yokota, T., Nishikawa, H., Ohkawa, Y., Kayama, H., Kallies, A., Nut, S. L., Sakaguchi, S., Takeda, K., Kurosaki, T., and Baba, Y.
    • Journal Title

      Immunity

      Volume: 41 Issue: 6 Pages: 1040-1051

    • DOI

      10.1016/j.immuni.2014.10.016

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potent functional uncoupling between STIM1 and Orai1 by dimeric 2-aminodiphenyl borinate analogs.2014

    • Author(s)
      Hendron E, Wang X, Zhou Y, Cai X, Goto J, Mikoshiba K, Baba Y, Kurosaki T, Wang Y, Gill DL.
    • Journal Title

      Cell Calcium.

      Volume: 56 Pages: 482-492

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] STIM1 Controls Neuronal Ca^<2+> Signaling, mGluR1-Dependent Synaptic Transmission, and Cerebellar Motor Behavior2014

    • Author(s)
      Hartmann. J., Karl, R.M., Alexander, R.P., Adelsberger, H., Brill, M.S., Ruhlmann, C., Ansel, A., Sakimura, K., Baba. Y., Kurosaki, T., Misgeld, T., Konnerth, A
    • Journal Title

      Neuron

      Volume: 82 Issue: 3 Pages: 635-44

    • DOI

      10.1016/j.neuron.2014.03.027

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of colonic IgA-secreting cells in the cecal patch2014

    • Author(s)
      Masahata, K., Umemoto, E., Kayama, H., Kotani, M., Nakamura, S., Kurakawa, T., Kikuta, J., Gotoh, K., Motooka, D., Sato, S., Higuchi, T., Baba, Y., Kurosaki, T., Kinoshita, M., Shimada, Y., Kimura, T., Okumura, R., Takeda, A., Tajima, M., Yoshie, O., Fukuzawa, M., Kiyono, H., Fagarasan, S., Iida, T., Ishii, M., Takeda, K
    • Journal Title

      Nature Comm

      Volume: 5 Issue: 1 Pages: 3704-3704

    • DOI

      10.1038/ncomms4704

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intrinsic disorder mediates cooperative signal transduction in STIM12014

    • Author(s)
      Furukawa, Y., Teraguchi, S., Ikegami, T., Dagliyan, O., Jin, L., Hall, D., Dokholyan, N.V., Namba, K., Akira, S., Kurosaki, T., Baba, Y., Standley, D.M.
    • Journal Title

      J Mol Biol

      Volume: 426 Issue: 10 Pages: 2082-97

    • DOI

      10.1016/j.jmb.2014.03.006

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense2014

    • Author(s)
      Zhang, H., Clemens, R.A., Liu, F., Hu, Y., Baba, Y., Theodore, P., Kurosaki, T., and Lowell, C.A.
    • Journal Title

      Blood

      Volume: 123 Issue: 14 Pages: 2238-49

    • DOI

      10.1182/blood-2012-08-450403

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense.2014

    • Author(s)
      Zhang H, Clemens RA, Liu F, Hu Y, Baba Y, Theodore P, Kurosaki T, Lowell CA.
    • Journal Title

      Blood

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcium signaling in B cells : Regulation of cytosolic Ca^<2+> increase and its sensor molecules, STIM1 and STIM22013

    • Author(s)
      Baba, Y., Matsumoto, M., Kurosaki, T
    • Journal Title

      Mol. Immunol

      Volume: 39 Issue: 2 Pages: 136-147

    • DOI

      10.1016/j.molimm.2013.10.006

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surf4 modulates STIMl-dependent calcium entry.2012

    • Author(s)
      Fujii y Baba Y
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 422 Pages: 615-620

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Regulatory function of B cells in autoimmune inflammation.2016

    • Author(s)
      馬場義裕
    • Organizer
      生医研セミナー
    • Place of Presentation
      九州大学
    • Year and Date
      2016-02-18
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Regulatory function of B cells in autoimmune inflammation2016

    • Author(s)
      馬場義裕
    • Organizer
      The 7th IFReC International Symposium "Immunology at the Forefront"
    • Place of Presentation
      Grand Front Osaka
    • Year and Date
      2016-01-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 炎症を制御するIL-10産生B細胞の誘導機序2015

    • Author(s)
      馬場義裕
    • Organizer
      第43回日本臨床免疫学総会
    • Place of Presentation
      神戸国際会議場、神戸
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] B細胞ストア作動性カルシウム流入による自己免疫性炎症反応の制御機構2015

    • Author(s)
      馬場義裕
    • Organizer
      日本薬学会第135回年会
    • Place of Presentation
      神戸学院大学(兵庫県、神戸)
    • Year and Date
      2015-03-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] B細胞におけるSOCEの生理的役割2013

    • Author(s)
      馬場義裕
    • Organizer
      第90回日本生理学会大会シンポジウム
    • Place of Presentation
      タワーホール船堀, 東京(招待講演)
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] The mechanism of calcium influx induced by ER calcium sensor STIM and its physiological function2012

    • Author(s)
      馬場義裕
    • Organizer
      第85回日本生化学学会大会シンポジウム
    • Place of Presentation
      福岡国際会議場, 福岡(招待講演)
    • Year and Date
      2012-12-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] Physiological significance for Calcium Influx in B cell2012

    • Author(s)
      馬場義裕
    • Organizer
      第40回日本臨床免疫学会シンポジウム
    • Place of Presentation
      京王プラザホテル, 東京(招待講演)
    • Year and Date
      2012-09-27
    • Related Report
      2012 Annual Research Report
  • [Book] B細胞ストア作動性カルシウム流入による自己免疫性炎症反応の制御機構2016

    • Author(s)
      馬場義裕
    • Total Pages
      5
    • Publisher
      薬学雑誌
    • Related Report
      2015 Annual Research Report
  • [Book] The Frontiers in Life Sciences B細胞による腫瘍制御2015

    • Author(s)
      馬場義裕
    • Total Pages
      10
    • Publisher
      南山堂
    • Related Report
      2015 Annual Research Report
  • [Book] 実験医学増刊号 自己免疫疾患: IL-10産生B細胞による自己免疫疾患の制御2015

    • Author(s)
      馬場義裕
    • Total Pages
      5
    • Publisher
      羊土社
    • Related Report
      2015 Annual Research Report
  • [Book] First Author's2014

    • Author(s)
      松本真典、黒崎知博、馬場義裕
    • Total Pages
      1
    • Publisher
      ライフサイエンス新着論文レビュー
    • Related Report
      2014 Annual Research Report
  • [Book] 臨床免疫・アレルギー科2013

    • Author(s)
      馬場義裕
    • Total Pages
      5
    • Publisher
      科学評論社
    • Related Report
      2013 Annual Research Report
  • [Book] YAKUGAKU ZASSHI2013

    • Author(s)
      松本真典、馬場義裕
    • Total Pages
      7
    • Publisher
      日本薬学会
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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