B lymphocytes as direct antigen-presenting cells for anti-tumor DNA vaccines

Oncotarget. 2016 Oct 18;7(42):67901-67918. doi: 10.18632/oncotarget.12178.

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.

Keywords: B cells; DNA vaccine; Immune response; Immunity; Immunology and Microbiology Section; dendritic cells; direct presentation.

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Coculture Techniques
  • DNA / genetics
  • DNA / immunology
  • DNA / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmids / genetics
  • Plasmids / immunology
  • Plasmids / metabolism
  • Sarcoma, Experimental / immunology
  • Sarcoma, Experimental / metabolism
  • Sarcoma, Experimental / pathology
  • Vaccines, DNA / immunology*

Substances

  • Cancer Vaccines
  • Vaccines, DNA
  • DNA