Abstract
BLys , a key cytokine that sustains B cell maturation and tolerance, binds three receptors: BR3, BCMA, and TACI. Results from knockout mice implicate a major functional role for BR3 and a redundant one for BCMA in B cell function. TACI's role is controversial based on defects in TI antibody responses accompanied by B cell hyperplasia in knockout mice. We have presently characterized a precise role for TACI in vivo. TACI(-/-) mice develop fatal autoimmune glomerulonephritis, proteinurea, and elevated levels of circulating autoantibodies. Treatment of B cells with TACI agonistic antibodies inhibits proliferation in vitro and activation of a chimeric receptor containing the TACI intracellular domain induces apoptosis. These results demonstrate the critical requirement for TACI in regulating B cell homeostasis.
MeSH terms
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Animals
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Apoptosis
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / pathology
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B-Cell Activation Factor Receptor
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Cell Differentiation
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Glomerulonephritis, Membranoproliferative / genetics
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Glomerulonephritis, Membranoproliferative / immunology
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Glomerulonephritis, Membranoproliferative / pathology
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Humans
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Lupus Erythematosus, Systemic / genetics
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Lupus Erythematosus, Systemic / immunology
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Lupus Erythematosus, Systemic / pathology
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / immunology*
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Lymphoproliferative Disorders / pathology
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Membrane Proteins*
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Mice
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Mice, Knockout
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Phenotype
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Protein Structure, Tertiary
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Receptors, Tumor Necrosis Factor / deficiency*
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Transmembrane Activator and CAML Interactor Protein
Substances
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B-Cell Activation Factor Receptor
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BLyS receptor
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Membrane Proteins
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Receptors, Tumor Necrosis Factor
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Recombinant Fusion Proteins
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TNFRSF13B protein, human
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TNFRSF13C protein, human
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Tnfrsf13b protein, mouse
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Tnfrsf13c protein, mouse
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Transmembrane Activator and CAML Interactor Protein