Elucidation of the antibody production mechanism for next-generation vaccine development

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokyo University of Science
• Principal Investigator: HARADA Yohsuke 東京理科大学, 付置研究所, 助教 (20328579)
• Co-Investigator(Kenkyū-buntansha): KUBO Masato 東京理科大学, 生命医科学研究所, 教授 (40277281)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: T細胞 / B細胞 / ワクチン / 抗体 / 免疫記憶

Outline of Final Research Achievements

It has been suggested that memory T follicular helper (Tfh) cells are generated and contribute to a secondary humoral response. Thus, to clarify the mechanisms for generation of memory Tfh cells is relevant for effective vaccine design. Here we demonstrate that Notch signaling regulates generation of memory Tfh cells. During contraction phase, up-regulation of CCR7 and down-regulation of CXCR5 brings Tfh cells into the T-B border area, where they are maintained as memory cells. Lack of Notch signaling during initial antigen priming, but not at the contraction phase, led to a failure of memory T cell generation due to abnormal migration caused by defective CCR7 up-regulation. Notch signaling regulated CCR7 expression through suppression of Blimp-1 expression. Our findings indicate that Notch signaling is critical for the generation and function of memory Tfh cells and could be a future target for the vaccination strategy.

Free Research Field

免疫学