日時 2017 年 11 月 9 日(木) 16:30~18:00 場所 東京理科大学生命医科学研究所2階大講義室
Speaker Hidehiro Yamane, PhD Cellular Immunology Section,
Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA
Mechanisms underlying the fine-tuning of CD4+ T cell positioning during T follicular helper cell differentiation
Abstract T follicular helper (TFH) cells are a subset of T helper cells that helps B cells produce immunoglobulin (Ig) and induce class switch recombination and somatic hypermutation in the Ig genes upon encounter with a T-dependent antigen (Ag). Differentiation of naïve CD4+ T cells into functional TFH cells involves not only a transcriptional regulation of signature TFH-related genes, a set of genes that drives TFH polarization program, but an alteration in the expression of chemoattractant receptors, integrins and their ligands, since a subcellular localization of Ag-primed CD4+ T cells in the secondary lymphoid organs is spaciotemporally regulated during TFH differentiation. We recently found that an E-box binding protein family of transcription factors HEB and Notch signaling pathway played crucial roles in the entry of Ag-primed CD4+ T cells that had undergone the TFH polarization program into B cell follicles and germinal centers, respectively, with little or no impact on the signature TFH-related gene expressions. Our findings shed a light to unappreciated functions of HEB and Notch pathway in fine-tuning the positioning of Ag-primed CD4+ T cells during the differentiation into functional TFH cells and may offer novel strategies for the development of effective antibody-based vaccines.