Abstract
The MerTK receptor tyrosine kinase is an important negative regulator of dendritic cell function and is required to prevent B cell autoimmunity in vivo. It is not currently known however, if any causal relationship exists between these two aspects of MerTK function. We sought to determine if dendritic cells (DC) from mice lacking MerTK (mertk(- / - ) mice) have characteristics that may aid in the development of B cell autoimmunity. Specifically, we found that mertk(- / - ) mice contain an elevated number of splenic DC, and this population contains an elevated proportion of cells secreting the critical B cell pro-survival factor, B cell activating factor (BAFF). Elevated numbers of BAFF-secreting cells were also detected among mertk(- / - ) bone marrow-derived dendritic cell (BMDC) populations. This was observed in both resting BMDC, and BMDC stimulated with lipopolysaccharide (LPS) or treated with exogenous apoptotic cells. We also found that DC in general have a pro-survival effect on resting B cells in co-culture. However, despite containing more BAFF-secreting cells, mertk(- / - ) BMDC were not superior to C57BL/6 or baff-deficient BMDC at promoting B cell survival. Furthermore, using decoy receptors, we show that DC may promote B cell survival and autoimmunity through a BAFF-and a proliferation-inducing ligand-independent mechanism.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Age Factors
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Animals
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Antibodies, Antinuclear / blood
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Antibodies, Antinuclear / immunology
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Autoimmunity / physiology
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B-Cell Activating Factor / blood
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B-Cell Activating Factor / metabolism*
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B-Cell Activating Factor / pharmacology
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B-Lymphocytes / cytology
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B-Lymphocytes / physiology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / drug effects
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Cell Count
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Cell Differentiation / drug effects
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Cell Survival / physiology
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Chromatin / immunology
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Coculture Techniques
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DNA / immunology
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / metabolism*
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Dendritic Cells, Follicular / cytology
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Dendritic Cells, Follicular / metabolism
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Gene Expression / genetics
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Interferon-gamma / pharmacology
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Proto-Oncogene Proteins / physiology*
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Receptor Protein-Tyrosine Kinases / physiology*
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Recombinant Proteins / pharmacology
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Spleen / cytology
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Spleen / metabolism
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Tumor Necrosis Factor Ligand Superfamily Member 13 / physiology
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c-Mer Tyrosine Kinase
Substances
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Antibodies, Antinuclear
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B-Cell Activating Factor
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Chromatin
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Lipopolysaccharides
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Proto-Oncogene Proteins
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Recombinant Proteins
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Tnfsf13 protein, mouse
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Tnfsf13b protein, mouse
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Tumor Necrosis Factor Ligand Superfamily Member 13
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Interferon-gamma
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DNA
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Mertk protein, mouse
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Receptor Protein-Tyrosine Kinases
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c-Mer Tyrosine Kinase