Abstract
Lupus-associated anti-DNA Abs display features of Ag selection, yet the triggering Ag in the disease is unknown. We previously demonstrated that the peptide DWEYSVWLSN is bound by a pathogenic anti-DNA Ab, and that immunization of nonautoimmune mice with this peptide induces autoantibodies and renal Ig deposition. To elucidate differences in the induced B cell responses in mice genetically predisposed to autoimmunity, young (NZB x NZW)F(1) mice were immunized with this peptide DNA mimetope. DWEYSVWLSN-immunized mice had significantly increased IgG anti-dsDNA, anti-laminin, and anti-cardiolipin Ab titers compared with controls. In addition, glomerular histopathology in the form of endocapillary disease and crescent formation was markedly more severe in DWEYSVWLSN-immunized mice. Analysis of mAbs from DWEYSVWLSN-immunized mice revealed that anti-peptide Abs were often cross-reactive with DNA. Genetic elements used in the Ab response in immunized mice were homologous to those used in the spontaneous anti-DNA response in (NZB x NZW)F(1) mice, as well as in other, experimentally induced anti-DNA Abs. Our results indicate that peptide immunization can induce a molecular genetic response common to a variety of stimuli that break tolerance to mammalian dsDNA. Based on the similarity between spontaneously arising anti-DNA Abs and several types of induced anti-DNA Abs, we suggest that there may be more than a single Ag that can trigger systemic lupus erythematosus.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Antinuclear / biosynthesis*
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Antibodies, Antinuclear / metabolism
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Clone Cells
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Cross Reactions
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DNA / immunology*
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Female
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Gene Rearrangement, B-Lymphocyte, Heavy Chain
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Gene Rearrangement, B-Lymphocyte, Light Chain
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Genetic Predisposition to Disease
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Immunoglobulin Variable Region / genetics
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Immunoglobulin kappa-Chains / genetics
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Injections, Subcutaneous
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Lupus Nephritis / genetics*
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Lupus Nephritis / immunology*
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Lupus Nephritis / pathology
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Mice
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Mice, Inbred NZB
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Molecular Mimicry / genetics
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Molecular Mimicry / immunology
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Molecular Sequence Data
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Oligopeptides / administration & dosage*
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Oligopeptides / immunology*
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Oligopeptides / metabolism
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology
Substances
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Antibodies, Antinuclear
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Immunoglobulin Variable Region
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Immunoglobulin kappa-Chains
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Oligopeptides
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Vaccines, DNA
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DNA
Associated data
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GENBANK/AF321931
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GENBANK/AF321932
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