Abstract
Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer-deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / immunology*
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Autoantibodies / blood
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Autoimmunity / immunology*
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B-Lymphocytes / immunology
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Cardiolipins / immunology
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Chromatin / immunology
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DNA / immunology
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Disease Models, Animal
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Female
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Fluorescent Dyes
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Glomerular Mesangium / pathology
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Immunoglobulin G / immunology
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Lupus Erythematosus, Systemic / complications
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Lupus Erythematosus, Systemic / immunology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Phagocytosis / immunology
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Protein-Tyrosine Kinases / deficiency*
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Protein-Tyrosine Kinases / genetics
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Proteinuria / complications
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Proteinuria / pathology
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Proto-Oncogene Proteins / deficiency*
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Proto-Oncogene Proteins / genetics
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Receptor Protein-Tyrosine Kinases*
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Rheumatoid Factor / blood
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Rhodamines
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c-Mer Tyrosine Kinase
Substances
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5-carboxytetramethylrhodamine succinimidyl ester
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Autoantibodies
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Cardiolipins
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Chromatin
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Fluorescent Dyes
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Immunoglobulin G
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Proto-Oncogene Proteins
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Rhodamines
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DNA
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Rheumatoid Factor
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Mertk protein, mouse
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Protein-Tyrosine Kinases
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Receptor Protein-Tyrosine Kinases
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c-Mer Tyrosine Kinase