B-lymphocytes in bone marrow or lymph nodes can take up plasmid DNA after intramuscular delivery.
Nucleic acid vaccines are an attractive alternative to conventional protein vaccines because of their ability to induce de novo production of antigens in a given tissue after DNA delivery. Although DNA vaccines are highly effective in inducing both cell-mediated and humoral immunity, little is known about the many cell types involved in plasmid DNA uptake in vivo. Here we demonstrate, for the first time, that plasmid DNA can be taken up by both bone marrow and lymph node B cells after intramuscular immunization. Plasmid DNA was also detected in CD11b+ and CD11c+ cells. This phenomenon was not restricted to plasmid DNA encoding mycobacterial 65-kd heat shock protein (pcDNA3-hsp65) because we observed similar results with plasmid-encoding green fluorescent protein (GFP-pEGFP-2C). In addition to plasmid DNA uptake, B cells also express the encoded protein, suggesting that B cells play a role in the immune response after DNA immunization. The biodistribution of plasmid DNA in B cells opens a new perspective in B-cell gene therapy for the in vivo use of plasmid DNA.
Coelho-Castelo
Arlete A M
AA
Department of Biochemistry and Immunology, University of São Paulo, 14049-900 São Paulo, Brazil.
Santos Júnior
Rubens R
RR
Bonato
Vânia L D
VL
Jamur
Maria Célia
MC
Oliver
Constance
C
Silva
Célio Lopes
CL
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D001854:Bone Marrow Cells; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D007273:Injections, Intramuscular; D008164:Luminescent Proteins; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D019444:Vaccines, DNA / Q000493:pharmacokinetics*
D008164:Luminescent Proteins; D019444:Vaccines, DNA; D049452:Green Fluorescent Proteins