Abstract
Both IL-21 and TLR agonists are important regulators of B cell responses, and the combination of IL-21 and TLR stimulation results in increased Ab production. However, it is not clear yet how IL-21 interacts with TLR signaling in B cells. In this study, we show that IL-21 enhances TLR-induced IgG production, whereas it has no effect on TLR-induced IL-6 production by human B cell cultures. These observations are explained by the finding that IL-21 augments TLR-induced IgG production via the TLR-MyD88-STAT3 pathway but not the classical TLR-MyD88-NF-κB pathway. We further demonstrate that stimulation of human B cells with IL-21 and TLR7/8 or TLR9 agonists increases the phosphorylation of STAT3, whereas the activation of NF-κB is not affected. Interestingly, like IL-21, IL-10 in combination with TLR signaling also enhances phosphorylation of STAT3, resulting in an increase of IgG production. Hence, IL-21 and IL-10 increase the activity of the TLR-MyD88-STAT3 pathway in human B cells via enhancing the phosphorylation of STAT3 for Ab production.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibody Formation
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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Cells, Cultured
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Humans
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / immunology
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Immunoglobulin M / biosynthesis
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Immunoglobulin M / immunology
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Interleukin-10 / immunology
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Interleukin-10 / metabolism*
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Interleukin-6 / biosynthesis
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Interleukins / agonists
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Interleukins / metabolism*
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Lymphocyte Activation
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Myeloid Differentiation Factor 88 / metabolism*
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NF-kappa B / metabolism
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Phosphorylation
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Positive Regulatory Domain I-Binding Factor 1
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Repressor Proteins / metabolism
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STAT3 Transcription Factor / metabolism*
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Signal Transduction
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Toll-Like Receptor 7 / agonists
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Toll-Like Receptor 7 / immunology
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Toll-Like Receptor 8 / agonists
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Toll-Like Receptor 8 / immunology
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Toll-Like Receptor 9 / agonists
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Toll-Like Receptor 9 / immunology
Substances
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Immunoglobulin G
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Immunoglobulin M
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Interleukin-6
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Interleukins
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MYD88 protein, human
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Myeloid Differentiation Factor 88
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NF-kappa B
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Repressor Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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TLR7 protein, human
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TLR8 protein, human
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TLR9 protein, human
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Toll-Like Receptor 7
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Toll-Like Receptor 8
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Toll-Like Receptor 9
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Interleukin-10
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PRDM1 protein, human
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Positive Regulatory Domain I-Binding Factor 1
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interleukin-21