Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Immunity. 2018 Oct 16;49(4):695-708.e4. doi: 10.1016/j.immuni.2018.08.012. Epub 2018 Oct 2.
B cells can present antigens to CD4 T cells, but it is thought that dendritic cells (DCs) are the primary initiators of naive CD4 T cell responses. Nanoparticles, including virus-like particles (VLPs), are attractive candidates as carriers for vaccines and drug delivery. Using RNA phage Qβ-derived VLP (Qβ-VLP) as a model antigen, we found that antigen-specific B cells were the dominant antigen-presenting cells that initiated naive CD4 T cell activation. B cells were sufficient to induce T follicular helper cell development in the absence of DCs. Qβ-specific B cells promoted CD4 T cell proliferation and differentiation via cognate interactions and through Toll-like receptor signaling-mediated cytokine production. Antigen-specific B cells were also involved in initiating CD4 T cell responses during immunization with inactivated influenza virus. These findings have implications for the rational design of nanoparticles as vaccine candidates, particularly for therapeutic vaccines that aim to break immune tolerance.
B 细胞可以向 CD4 T 细胞呈递抗原，但人们认为树突状细胞（DC）是初始 CD4 T 细胞反应的主要启动者。纳米颗粒，包括病毒样颗粒（VLPs），作为疫苗和药物递送的载体很有吸引力。我们使用 RNA 噬菌体 Qβ衍生的 VLP（Qβ-VLP）作为模型抗原，发现抗原特异性 B 细胞是启动初始 CD4 T 细胞活化的主要抗原呈递细胞。在没有 DC 的情况下，B 细胞足以诱导滤泡辅助性 T 细胞的发育。Qβ特异性 B 细胞通过同源相互作用和 Toll 样受体信号转导介导的细胞因子产生促进 CD4 T 细胞的增殖和分化。在灭活流感病毒免疫接种过程中，抗原特异性 B 细胞也参与启动 CD4 T 细胞反应。这些发现对于合理设计纳米颗粒作为疫苗候选物具有重要意义，特别是对于旨在打破免疫耐受的治疗性疫苗。
