Development of efficient induction method of human regulatory B cells

• Project/Area Number: 16K15217
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kyushu University (2017-2018); Osaka University (2016)
• Principal Investigator: Baba Yoshihiro 九州大学, 生体防御医学研究所, 教授 (20415269)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 制御生B細胞 / I型インターフェロン / B細胞 / IL-10 / ヒト / 制御性B細胞

Outline of Final Research Achievements

In recent years, the presence of IL-10 producing B cells (regulatory B cells) that suppress immune diseases and inflammation has been shown. However, "the nature of human regulatory B cells and their differentiation process" are still unknown. To understand these questions, in this study, we examined the gene expression of human regulatory B cells and clarified the gene expression pattern characteristic of this subset. In addition, we identified the precursor cells of human regulatory B cells. We also developed a culture method that can amplify human regulatory B cells efficiently.

Academic Significance and Societal Importance of the Research Achievements

従来、B 細胞は自己免疫や炎症を悪化させる要因としてのみ捉えられてきたが、必ずしもそう ではなく、負の制御を行うことが認知されつつある。本研究は、制御性B細胞の特徴づけは本分野に新機軸を与える研究になることが期待される。さらに、ヒト制御性B細胞の実体解明により、新たな疾患診断法への発展が期待される。また、ヒト制御性B細胞の誘導技術は将来の輸注療法や疾患病態の相関を検証する手段を提供すると予想され、免疫や炎症疾患の理解や新しい治療戦略として大きな可能性をもちと思われる。

Research Products

• [Journal Article] The COMMD3/8 complex is a determinant of GRK6 specificity for chemoattractant receptors. (2019)
  • Author(s): Nakai A, Fujimoto J, Haruhiko M, Stumm R, Narazaki M, Schulz S, Baba Y, Kumanogoh A, Suzuki K.
  • Journal Title: J. Exp. Med. Volume: in press
  • Peer Reviewed
• [Journal Article] Sensitive detection of fluorescence in western blotting by merging images (2018)
  • Author(s): Kondo Yukari、Higa Shinichiro、Iwasaki Takeshi、Matsumoto Tomoya、Maehara Kazumitsu、Harada Akihito、Baba Yoshihiro、Fujita Masatoshi、Ohkawa Yasuyuki
  • Journal Title: PLOS ONE Volume: 13 Issue: 1 Pages: 0191532-0191532
  • DOI: 10.1371/journal.pone.0191532
  • Peer Reviewed / Open Access
• [Journal Article] Stromal interaction molecule 1 haploinsufficiency causes maladaptive response to pressure overload. (2017)
  • Author(s): Ohba T, Watanabe H, Murakami M, Iino K, Adachi T, Baba Y, Kurosaki T, Ono K, Ito H.
  • Journal Title: PLoS One Volume: 12
  • Peer Reviewed / Open Access
• [Journal Article] The activated conformation of integrin β7 as a target for multiple myeloma-specific chimeric antigen receptor T cell therapy. (2017)
  • Author(s): Hosen N, Matsunaga Y, Hasegawa K, Matsuno H, Nakamura Y, Makita M, Watanabe K, Yoshida M, Satoh K, Morimoto S, Fujiki F, Nakajima H, Nakata J, Nishida S, Tsuboi A, Oka Y, Manabe M, Ichihara H, Aoyama Y, Mugitani A, Nakao T, Hino M, Uchibori R, Ozawa K, Baba Y, et al.
  • Journal Title: Nat. Med. Volume: 23 Issue: 12 Pages: 1436-1443
  • DOI: 10.1038/nm.4431
  • Peer Reviewed
• [Journal Article] UDP-Induced Phagocytosis and ATP-Stimulated Chemotactic Migration Are Impaired in STIM1-/- Microglia In Vitro and In Vivo. (2017)
  • Author(s): Lim HM, Woon H, Han JW, Baba Y, Kurosaki T, Lee MG, Kim JY.
  • Journal Title: Mediators Inflamm. Volume: 2017 Pages: 8158514-8158514
  • DOI: 10.1155/2017/8158514
  • Peer Reviewed
• [Journal Article] LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation. (2016)
  • Author(s): Morimoto K, Baba Y, Shinohara H, Kang S, Nojima S, Kimura T, Ito D, Yoshida Y, Maeda Y, Sarashina-Kida H, Nishide M, Hosokawa T, Kato Y, Hayama Y, Kinehara Y, Okuno T, Takamatsu H, Hirano T, Shima Y, Narazaki M, Kurosaki T, Toyofuku T, Kumanogoh A.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 25738-25738
  • DOI: 10.1038/srep25738
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Humoral immunity and diseases (2018)
  • Author(s): 馬場義裕
  • Organizer: 第47回日本免疫学会
  • Invited
• [Presentation] B細胞による炎症制御機構 (2018)
  • Author(s): 馬場義裕
  • Organizer: 第 9 回中国免疫不全症研究会
  • Invited
• [Book] 制御性B細胞と疾患 (2018)
  • Author(s): 川上亮、馬場義裕
  • Publisher: 先端医学社 炎症と免疫
• [Book] 免疫ペディア 「B細胞抗原受容体」「抗原ー抗体反応と免疫複合体」「抗体のクラススイッチ」「抗体の多様性」 (2017)
  • Author(s): 馬場義裕
  • Total Pages: 12
  • Publisher: 羊土社
• [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