The Role of G5PR and Fc gamma RIIB in the development of autoimmune disease

• Project/Area Number: 25860813
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Kumamoto University
• Principal Investigator: KITABATAKE Masahiro 熊本大学, 生命科学研究部, 助教 (60457588)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 自己抗体 / B-1細胞 / 胚中心 / 自己免疫疾患

Outline of Final Research Achievements

Autoimmunity is associated with the generation of high affinity auto-antibodies (Abs) that are strongly reactive to self-antigens and class switching, typically with IgG class Abs produced by long-lived plasma cells. Peritoneal B-1a cells, which often produce the IgM class Abs cross-react with self-Ag, are thought to be the source of auto-Ab-producing long-lived plasma cells because various autoimmune-prone mice show the abnormal expansion of peritoneal B-1a cells. In this study, we demonstrated that B-1a cells could differentiate into IgG auto-Ab producing plasma cells in the germinal center like environment. In addition, abnormal expression of G5PR, which is regulatory molecule for B cell receptor signaling, enhanced the differentiation of B-1a cells into auto-Ab producing cells . Thus, the regulation of cell signaling by G5PR in B-1a cells might be a critical target to prevent auto-Ab production in autoimmune diseases.

Research Products

• [Journal Article] JNK Regulatory Molecule G5PR Induces IgG Autoantibody-Producing Plasmablasts from Peritoneal B1a Cells. (2015)
  • Author(s): Kitabatake M, Soma M, Zhang T, Kuwahara K, Fukushima Y, Nojima T, Kitamura D, Sakaguchi N.
  • Journal Title: J Immunol. Volume: 194 Issue: 4 Pages: 1480-1488
  • DOI: 10.4049/jimmunol.1401127
  • Peer Reviewed / Open Access
• [Journal Article] Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus. (2014)
  • Author(s): Yasui F, Kohara M, Kitabatake M, Nishiwaki T, Fujii H, Tateno C, Yoneda M, Morita K, Matsushima K, Koyasu S, Kai C
  • Journal Title: Virology Volume: 454-455 Pages: 157-168
  • DOI: 10.1016/j.virol.2014.02.005
  • Peer Reviewed / Open Access
• [Journal Article] Breast cancers with high DSS1 expression that potentially maintains BRCA2 stability have poor prognosis in the relapse-free survival (2013)
  • Author(s): Rezano A, Kuwahara K, Yamamoto-Ibusuki M, Kitabatake M, Moolthiya P, Phimsen S, Suda T, Tone S, Yamamoto Y, Iwase H, Sakaguchi N
  • Journal Title: BMC Cancer Volume: 13 Issue: 1 Pages: 562-562
  • DOI: 10.1186/1471-2407-13-562
  • Peer Reviewed
• [Presentation] JNK regulatory molecule G5PR induces peritoneal B1a cells into IgG autoantibody-producing plasmablasts (2014)
  • Author(s): Kitabatake Masahiro, Soma Miho, Zhang Tianli, Nojima Takuya, Kitamura Daisuke, Sakaguchi Nobuo
  • 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
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Highly pathogenic avian influenza A H5N1 virus causes severe symptoms due to insufficient induction of humoral immune response. (2014)
  • Author(s): Ikejiri Ai, Yasui Fumihiko, Itoh Ysushi, Kitabatake Masahiro, Sakaguchi Nobuo, Ogasawara Kazumasa, Kohara Michinori.
  • 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
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Protein phosphatase subunit G5PR regulates the plasmablast differentiation and autoantibody production of peritoneal B1a cells
  • Author(s): Masahiro Kitabatake, Tianli Zhang , Kazuhiko Kuwahara, and Nobuo Sakaguchi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 千葉