Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA.
To investigate the role of antigen drive in anti-double-stranded (ds) DNA production, the antibody response induced in lupus-prone NZB/NZW mice by E. coli (EC) dsDNA was evaluated. Preautoimmune NZB/NZW female mice were immunized with complexes of EC dsDNA with methylated bovine serum albumin (mBSA) in complete Freund's adjuvant; control mice received either mBSA complexes with calf thymus (CT) dsDNA or mBSA alone in adjuvant. IgG antibody responses were assessed by ELISA. Similar to normal mice, immunized NZB/NZW mice produced significant levels of anti-dsDNA when measured with EC dsDNA as antigen. Whereas normal mice produce antibodies which are specific for the immunizing bacterial DNA, NZB/NZW mice produced antibodies that bound crossreactively to CT dsDNA by ELISA. Furthermore, the induced antibodies resembled lupus anti-DNA in their fine specificity for polynucleotide antigens and reactivity with Crithidia luciliae DNA. Despite their response to EC dsDNA, NZB/NZW mice immunized with CT dsDNA failed to generate significant anti-dsDNA responses. These results provide further evidence for the enhanced immunogenicity of bacterial DNA and suggest that immune cell abnormalities in NZB/NZW mice promote the generation of crossreactive autoantibody responses when confronted with a foreign DNA.
Gilkeson
G S
GS
Medical Research Service, Durham VA Medical Center, North Carolina 27705.
Pippen
A M
AM
Pisetsky
D S
DS
D000375:Aging / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity / Q000276:immunology; D003421:Crithidia / Q000235:genetics / Q000276:immunology; D003429:Cross Reactions; D003433:Crosses, Genetic; D004269:DNA, Bacterial / Q000276:immunology*; D016054:DNA, Protozoan / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D013045:Species Specificity
D001323:Autoantibodies; D004269:DNA, Bacterial; D016054:DNA, Protozoan