报告题目: Novel Immune Activating Mechanisms of Pathogen-Like Nanoparticle Antigen
报告人 :侯百东 研究员,中国科学院生物物理所
报告时间: 2019年3月26日10:00-11:30
报告地点:生科院二楼大会议室
邀请人 :李子福 教授
专家简介
侯百东研究员,现任中国科学院生物物理所,感染与免疫中心重点实验室课题组组长。本科毕业于北京医科大学(现北京大学医学部),博士毕业于北京协和医科大学,随后分别在范德比尔特大学和加州大学旧金山分校从事博士后研究。2009-2011在加州大学旧金山分校任助理研究员,2011年受聘为中国科学院生物物理所研究员。其研究方向包括B淋巴细胞和抗体反应、纳米颗粒抗原/疫苗的免疫反应机理、Toll样受体等天然免疫识别受体信号在免疫细胞发育和分化、粘膜免疫、抗感染免疫、和自身免疫中作用的机制。研究成果发表于Immunity,Nat Immunol,J Exp Med, Blood,PNAS.,J Immunol,Am J Respir Cell Mol Biol,PLoS Pathog,Cell Mol Immunol,J Virol,Immunological Reviews等杂志。
摘要:
Nanoparticles assembled from viral coat proteins, termed virus-like particles (VLPs), are commonly used as carriers for vaccines and drug delivery. However, despite the growing popularity of these bio-reagents in medical use, our understanding of the mechanisms by which they interact with the immune system in vivo is still very limited. Indeed, it has been generally assumed that these antigens are taken up by dendritic cells (DCs) to initiate the T cell response. In studying the immune responses to a RNA-phage-derived VLP antigen, we found surprisingly that antigen-specific B cells, instead of DCs, were the primary antigen presenting cells that initiate the CD4+ T cell activation upon immunization. Although antigen-specific B cells only account for a very small fraction of the total B cells, they nevertheless captured the VLP efficiently, and induced robust cell proliferation and differentiation of naïve CD4+ T cells by presenting cognate antigens and producing cytokines downstream of the Toll-like receptor signaling in B cells. Furthermore, we found that this function of B cells may play a role in bypassing the suppression on DC function by regulatory T cells and inducing immune response to tolerized antigen. Our finding that B cells act as the dominant antigen-presenting cells to initiate CD4 T cell response under the physiological condition will provide insights for developing novel prophylactic and therapeutic vaccines.