Specificity and immunochemical properties of anti-DNA antibodies induced in normal mice by immunization with mammalian DNA with a CpG oligonucleotide as adjuvant.
To elucidate the role of DNA antigen drive in the anti-DNA response, the specificity and immunochemical properties of anti-DNA antibodies induced in normal mice by immunization with double stranded (ds) mammalian DNA with a CpG oligonucleotide (ODN) adjuvant were characterized. Like spontaneous anti-DNA from MRL/lpr mice, the induced anti-DNA bound cross-reactively to DNA from five different species by ELISA. The induced antibodies displayed a predominance of IgG2a and had much lower amount of IgG3 than spontaneous antibodies. Surface plasmon resonance indicated that the induced and spontaneous anti-DNA antibodies have a similar range of avidity and binding kinetics. While sera from the MRL/lpr mice had substantial binding to histones and nucleosomes, the immunized mice had antibody levels to these antigens similar to those of mice treated only with incomplete Freund's adjuvant. Together, these results indicate that normal mice can produce autoantibodies to dsDNA, with a CpG ODN allowing the generation of antibodies resembling those in spontaneous autoimmunity.
Tran
Trinh T
TT
Division of Rheumatology, Duke University Medical Center, Durham, NC 27709, USA.
Reich
Charles F
CF
Alam
Munir
M
Pisetsky
David S
DS
D000276:Adjuvants, Immunologic; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex / Q000276:immunology; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006657:Histones / Q000276:immunology; D007114:Immunization; D007132:Immunoglobulin Isotypes; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009707:Nucleosomes / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D020349:Surface Plasmon Resonance
D000276:Adjuvants, Immunologic; D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; C408982:CPG-oligonucleotide; D006657:Histones; D007132:Immunoglobulin Isotypes; D009707:Nucleosomes; D009838:Oligodeoxyribonucleotides; D004247:DNA