title: TLR9-independent activation of B lymphocytes by bacterial DNA.
abstract: The intracellular Toll-like receptor 9 (TLR9) is unique in its ability to recognize single-stranded DNA unmethylated at CpG motifs. Work from this laboratory showed that plasmid DNA is spontaneously internalized in B lymphocytes. This event is followed by the upregulation of costimulatory molecules and the acquisition of antigen presenting function by these cells. However, it is not known whether this phenomenon depends on TLR9. Because of the relevant role played by DNA-based drugs in immunotherapy and vaccination, and the central role of TLR9 signaling by CpG motifs, we decided to investigate whether signaling through TLR9 is a prerequisite for spontaneous transgenesis of lymphocytes. Here we found that transgene expression and upregulation of CD40 and CD86 costimulatory molecules was not inhibited by chloroquine treatment. Spontaneous transgenesis also occurred in B lymphocytes from TLR9-/- mice, and the injection of TLR9-/- transgenic B lymphocytes in C57Bl/6 mice induced both CD4 and CD8 T cell responses comparable to those induced by wild-type B lymphocytes. Collectively, these results suggest that plasmid DNA activates mammalian B lymphocytes through a TLR9 independent pathway.
authors.affiliation: The Laboratory of Immunology, Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, California 92093-0837, USA.
authors.forename: Xochitl
authors.initials: X
authors.lastname: Cortez-Gonzalez
authors.forename: Ilenia
authors.initials: I
authors.lastname: Pellicciotta
authors.forename: Mara
authors.initials: M
authors.lastname: Gerloni
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wheeler
authors.forename: Paola
authors.initials: P
authors.lastname: Castiglioni
authors.forename: Petar
authors.initials: P
authors.lastname: Lenert
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zanetti
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D004269:DNA, Bacterial / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D019076:Transgenes; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D004269:DNA, Bacterial; D051217:Toll-Like Receptor 9