title: B lymphocytes as direct antigen-presenting cells for anti-tumor DNA vaccines.
abstract: In spite of remarkable preclinical efficacy, DNA vaccination has demonstrated low immunogenicity in humans. While efforts have focused on increasing cross-presentation of DNA-encoded antigens, efforts to increase DNA vaccine immunogenicity by targeting direct presentation have remained mostly unexplored. In these studies, we compared the ability of different APCs to present antigen to T cells after simple co-culture with plasmid DNA. We found that human primary peripheral B lymphocytes, and not monocytes or in vitro derived dendritic cells (DCs), were able to efficiently encode antigen mRNA and expand cognate tumor antigen-specific CD8 T cells ex vivo. Similarly, murine B lymphocytes co-cultured with plasmid DNA, and not DCs, were able to prime antigen-specific T cells in vivo. Moreover, B lymphocyte-mediated presentation of plasmid antigen led to greater Th1-biased immunity and was sufficient to elicit an anti-tumor effect in vivo. Surprisingly, increasing plasmid presentation by B cells, and not cross presentation of peptides by DCs, further augmented traditional plasmid vaccination. Together, these data suggest that targeting plasmid DNA to B lymphocytes, for example through transfer of ex vivo plasmidloaded B cells, may be novel means to achieve greater T cell immunity from DNA vaccines.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.|Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Viswa Teja
authors.initials: VT
authors.lastname: Colluru
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.|Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: McNeel
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004247:DNA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010957:Plasmids / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D019444:Vaccines, DNA; D004247:DNA
keywords: B cells; DNA vaccine; Immune response; Immunity; Immunology and Microbiology Section; dendritic cells; direct presentation