The analysis of development of autoimmune disease and abnormalexpansion of B-1 cells in G5PR transgenic mice

2012 Fiscal Year Final Research Report

• Project/Area Number: 23791116
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: 膠原病・アレルギー・感染症内科学
• 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): 2011 – 2012
• Keywords: 膠原病学 / 自己免疫疾患 / B-1 細胞 / 抗原受容体シグナル

Research Abstract

In the autoimmune disease, auto-reactive B cells are activated and produce theautoantibodies, which induce the tissue injury. We found that abnormal expression of G5PR,one of the B’’ regulatory subunit of the serine/threonine protein phosphatase 2A,induced the expansion of B-1a cells in the peritoneal cavity and generation ofautoantibodies in mice. Over-expression of G5PR in B-1a cells suppressed the JNK-mediatedapoptotic signal pathway and rescued from activation-induced cell death by antigenstimulation. These results suggest that G5PR may play a pivotal role in B cell selectionfor B-1a cells and in the development of autoimmune disease.

Research Products

• [Journal Article] Lyn signaling to upregulate GANP iscritical for the survival ofhigh-affinity B cells in germinalcenters of lymphoid organs (2012)
  • Author(s): Kuwahara Kazuhiko, Nakaya Teruo,Phimsen Suchada, Toda Teppei,Kitabatake Masahiro, Kaji Tomohiro,Takemori Toshitada, Watanabe Takeshi,and Sakaguchi Nobuo
  • Journal Title: Journal of Immunology Volume: 189巻 Pages: 3472-3479
  • DOI: DOI:10.4049/jimmunol.1200649
  • Peer Reviewed
• [Journal Article] Transgenic overexpression of G5PR thatis normally augmented in centrocytesimpairs the enrichment ofhigh-affinity antigen-specific Bcells, increases peritoneal B-1a cells,and induces autoimmunity in agedfemale mice (2012)
  • Author(s): Kitabatake Masahiro, Toda Teppei,Kuwahara Kazuhiko, Igarashi Hideya,Ohtsuji Mareki, Tsurui Hiromichi,Hirose Sachiko, and Sakaguchi Nobuo
  • Journal Title: Journal of Immunology Volume: 189巻 Pages: 1193-1201
  • DOI: DOI:10.4049/jimmunol.1102774
  • Peer Reviewed
• [Journal Article] Selective cell death ofp53-insufficient cancer cells isinduced by knockdown of the mRNA exportmolecule GANP (2012)
  • Author(s): Phimsen Suchada, Kuwahara Kazuhiko,Nakaya Teruo, Ohta Kazutaka, SudaTaiji, Rezano Andri, KitabatakeMasahiro, Vaeteewoottacharn Kulthida,Okada Seiji, Tone Shigenobu, andSakaguchi Nobuo
  • Journal Title: Apoptosis Volume: 17巻 Pages: 679-690
  • DOI: DOI:10.1007/s10495-012-0711-8
  • Peer Reviewed
• [Presentation] Survival of antigen-driven germinalcenter B-cell is controlled bycentrocyte-associated expression ofapoptosis-regulator G5PR (2012)
  • Author(s): 北畠正大、他
  • Organizer: 第41回日本免疫学会学術集
  • Place of Presentation: 神戸国際会議場(兵庫)
  • Year and Date: 2012-12-07
• [Presentation] An apoptotic regulator G5PR is highlyexpressed in centrocytes andcritical for B cell survival in mice (2011)
  • Author(s): 北畠正大、他
  • Organizer: 第40回日本免疫学会学術集
  • Place of Presentation: 幕張メッセ(千葉)
  • Year and Date: 2011-11-26
• [Book] 臨床免疫・アレルギー科 57巻「自己免疫疾患とB1細胞」 (2012)
  • Author(s): 北畠正大、阪口薫雄
  • Total Pages: 125-132
  • Publisher: 科学評論社
• [Remarks] ホームページ
  • URL: http://www.k-immu.jp/ja/index.html