A study of the regulational mechanisms for IgE+ B cell development and maintenance

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293116
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Tokyo University of Science
• Principal Investigator: KITAMURA DAISUKE 東京理科大学, 研究推進機構生命医科学研究所, 教授 (70204914)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 免疫学 / 獲得免疫 / アレルギー / IgE / 胚中心 / シグナル伝達 / 免疫記憶

Outline of Final Research Achievements

IgE is critical in the pathogenesis of allergic diseases, but it emerge only transiently during the immune response and kept low in healthy individuals. B cells switch to IgE in germinal center (GC), but that the IgE+ B cells immediately become short-lived plasma cells (PCs) and not differentiate into long-lived (LL) PCs or memory B cells. We found that the expression of membrane IgE (mIgE) spontaneously induces PC differentiation and apoptosis through signaling pathways from Syk via BLNK or CD19. Notably, mIgE binds to CD19 and activates CD19-PI3kinase-Akt pathway leading to the PC differentiation. In the BLNK-deficient mice, IgE+ GC and memory B cells remained high in number during immune response, and more IgE+ LLPCs and serum IgE were produced, rendering the mice hypersensitive to a secondary challenge. A similar phenotype was also observed in CD19+/- mice. These results suggest that somatic defects of the mIgE signaling pathways through BLNK and CD19 can cause allergic diseases.

Free Research Field

免疫学