Abstract
The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles systemic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of alloreactive T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain site-directed transgenic mouse strains. This resulted in clonal expansion and selection of specific mutations in the anti-double-stranded (ds) DNA B cell population. These data, together with a high frequency of anti-dsDNA B cell clones recovered as hybridomas, suggested that anti-dsDNAs are the product of an antigen-driven immune response. Genetic analysis associated this response with the generation of anti-dsDNA B cells through secondary rearrangements that replaced the site-directed transgene (sd-tg) with endogenous VH genes.
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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Amino Acid Sequence
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Animals
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Antibodies, Antinuclear / chemistry
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Antibodies, Antinuclear / genetics*
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Antibodies, Antinuclear / immunology*
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Antibodies, Monoclonal / immunology
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Antibody Specificity
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B-Lymphocytes / immunology*
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Base Sequence
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DNA / immunology*
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Enzyme-Linked Immunosorbent Assay
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Gene Rearrangement, B-Lymphocyte / genetics
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Graft vs Host Disease / immunology
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Hybridomas / immunology
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Hybridomas / metabolism
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Immunoglobulin Allotypes / chemistry
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Immunoglobulin Allotypes / genetics
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Immunoglobulin Allotypes / immunology
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Immunoglobulin G / genetics
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Immunoglobulin G / immunology
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / genetics*
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Immunoglobulin Heavy Chains / immunology*
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Immunoglobulin Light Chains / chemistry
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Immunoglobulin Light Chains / genetics
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Mutation / genetics
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Transgenes / genetics
Substances
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Antibodies, Antinuclear
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Antibodies, Monoclonal
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Immunoglobulin Allotypes
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Immunoglobulin Light Chains
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DNA