Dominant roles of B cells in the initiation of CD4 T cell response to a virus-derived nanoparticle antigen. Dominant roles of B cells in the initiation of CD4 T cell response to a virus-derived nanoparticle antigen

Nanoparticles, including virus-like particles (VLP), are attractive candidates as carriers for vaccines and drug delivery. However, little is known about how they are targeted to the immune system in vivo. Using RNA phage Qb-derived VLP (Qb-VLP) as a model antigen, we found surprisingly that antigen-specific B cells, instead of dendritic cells (DCs), were the dominant antigen presenting cells that initiate the naïve CD4 T cell activation, and were sufficient to induce T follicular helper cell development in the absence of DCs. Qb-specific B cells promoted CD4 T cell proliferation by providing cognate interactions and cell differentiation by generating cytokine milieu which depended on the Toll-like receptor signaling in B cells. Moreover, antigen-specific B cells were also involved in initiating CD4 T cell response to influenza virus. The mechanism revealed here will advance the rational design of nanoparticles as vaccine candidates, especially for therapeutic vaccines that aim to break immune tolerance. Overall design: We measured expression profiles by RNA-seq in naïve B cells and Qb-VLP-activated B cells including plasma cells (PC).