Abstract
B lymphocyte stimulator (BLyS), also known as B cell-activating factor, is a key positive regulator of B cell homeostasis, and elevated levels of BLyS have been observed in systemic lupus erythematosus (SLE) patients. Given that anti-chromatin auto-antibodies are one of the hallmarks of SLE, we examined the role of BLyS and its receptors in the regulation of anti-chromatin B cells. We demonstrate that exogenous BLyS treatment leads to an increase in B cell numbers, particularly anti-chromatin B cells; yet, their localization in the spleen and auto-antibody production remain unaffected. We also examined transmembrane activator and CAML interactor (TACI), BLyS receptor 3 (BR3) and B cell maturation antigen expression on anti-chromatin B cells before and after receiving T cell help. Interestingly, in the absence of T cell help, TACI expression is greater on immature anti-chromatin B cells compared with immature Tg(-) B cells, whereas BR3 levels are comparable. After receiving T cell help, the anti-chromatin B cells that have differentiated into short-lived plasma cells no longer express BR3 but retain TACI. These data suggest a novel role for TACI in anti-chromatin B cell homeostasis and differentiation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Antinuclear / blood
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Antibodies, Antinuclear / immunology*
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Antibody Formation / drug effects
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Antibody Formation / immunology
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B-Cell Activating Factor / pharmacology*
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B-Cell Activation Factor Receptor / genetics
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B-Cell Activation Factor Receptor / metabolism
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B-Cell Maturation Antigen / genetics
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B-Cell Maturation Antigen / metabolism
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B-Lymphocyte Subsets / drug effects
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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B-Lymphocytes / drug effects*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Female
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Gene Expression
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Hemagglutinin Glycoproteins, Influenza Virus / genetics
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Hemagglutinin Glycoproteins, Influenza Virus / metabolism
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin kappa-Chains / genetics
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Mice, Transgenic
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Receptors, CXCR5
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Receptors, Chemokine / genetics
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Receptors, Chemokine / metabolism
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / metabolism*
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Spleen / cytology
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Spleen / drug effects
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Spleen / immunology
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / transplantation
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Transmembrane Activator and CAML Interactor Protein / genetics
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Transmembrane Activator and CAML Interactor Protein / metabolism
Substances
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Antibodies, Antinuclear
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B-Cell Activating Factor
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B-Cell Activation Factor Receptor
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B-Cell Maturation Antigen
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BLyS receptor
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CXCR5 protein, mouse
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Hemagglutinin Glycoproteins, Influenza Virus
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Immunoglobulin Heavy Chains
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Immunoglobulin kappa-Chains
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Receptors, CXCR5
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Receptors, Chemokine
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Receptors, Tumor Necrosis Factor
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Tnfrsf13b protein, mouse
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Tnfrsf17 protein, mouse
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Transmembrane Activator and CAML Interactor Protein