Department of BioMedical Research, University of Bern, Bern, Switzerland.
Department of Immunology RIA, University Hospital Bern, Bern, Switzerland.
Front Immunol. 2019 Apr 5;10:736. doi: 10.3389/fimmu.2019.00736. eCollection 2019.
Secondary plasma cells (PCs) originate from memory B cells and produce increased levels of antibodies with higher affinity compared to PCs generated during primary responses. Here we demonstrate that virus-like particles (VLPs) only induce secondary PCs in the presence of toll-like receptor (TLR) 7 and if they are loaded with RNA. Furthermore, adoptive transfer experiments demonstrate that RNA and TLR7 signaling are required for secondary PC generation, both at the level of memory B cell as well as PC differentiation. TLR7-signaling occurred in a B cell intrinsic manner as TLR7-deficient B cells in an otherwise TLR7-competent environment failed to differentiate into secondary PCs. Therefore, RNA inside VLPs is essential for the generation of memory B cells, which are competent to differentiate to secondary PCs and for the differentiation of secondary PCs themselves. While we have not tested all other TLR or non-TLR adjuvants with our VLPs, these data have obvious implications for vaccine design, as RNA packaged into VLPs is a simple way to enhance induction of memory B cells capable of generating secondary PCs.
次级浆细胞（PCs）起源于记忆 B 细胞，与初次应答中产生的 PCs 相比，其产生的抗体具有更高的亲和力和更高的水平。在这里，我们证明了只有在存在 Toll 样受体（TLR）7 的情况下，病毒样颗粒（VLPs）才会诱导次级 PCs 的产生，如果它们负载有 RNA。此外，过继转移实验表明，RNA 和 TLR7 信号对于次级 PC 的产生是必需的，无论是在记忆 B 细胞还是 PC 分化水平上。TLR7 信号发生在 B 细胞内在的方式中，因为在其他 TLR7 功能正常的环境中缺乏 TLR7 的 B 细胞不能分化为次级 PCs。因此，VLPs 内的 RNA 对于记忆 B 细胞的产生是必需的，这些记忆 B 细胞有能力分化为次级 PCs，并分化为次级 PCs 本身。虽然我们没有用我们的 VLPs 测试所有其他 TLR 或非 TLR 佐剂，但这些数据对疫苗设计具有明显的意义，因为封装在 VLPs 中的 RNA 是增强诱导能够产生次级 PCs 的记忆 B 细胞的一种简单方法。
