Krüger, Caroline C.; Thoms, Franziska; Keller, Elsbeth; Leoratti, Fabiana M. S.; Vogel, Monique; Bachmann, Martin F. (2019). RNA and Toll-Like Receptor 7 License the Generation of Superior Secondary Plasma Cells at Multiple Levels in a B Cell Intrinsic Fashion. Frontiers in immunology, 10(736), p. 736. Frontiers Research Foundation 10.3389/fimmu.2019.00736
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Krueger et al. fimmu-10-00736.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (4MB) | Preview |
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 ofmemory 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.
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