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DNA vaccines have shown limited effectiveness in cancer treatment, and B cells rather than dendritic cells (DCs) have been found to be the primary antigen-presenting cells (APCs) after passive uptake of plasmid DNA. This study aimed to understand the requirements for B cells to present DNA-encoded antigens and enhance the immunogenicity of plasmid DNA vaccines. The study used ovalbumin-specific CD8+ T cells and isolated APC populations to demonstrate that B cells, but not DCs, can translate the encoded antigen after passive uptake of plasmid DNA. However, CD8+ T cells were only activated when B cells were co-cultured with DCs, indicating the necessity of cell-cell contact between B cells and DCs. Through further investigations using MHCI knockout and re-purification studies, it was confirmed that B cells serve as the primary APCs, while DCs play a licensing role. Additionally, the gene expression profiles of licensed B cells differed significantly from unlicensed B cells and resembled those of B cells activated with a TLR7/8 agonist. These findings highlight the importance of studying B cells as APCs to enhance the efficacy of DNA vaccines.
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