Abstract
IL-21 induces the differentiation of activated B lymphocytes into plasma cells (PC), but its direct effect on PC remains uncertain. This study analyzes the role of IL-21 on human in vivo-generated PC. IL-21R was clearly expressed on PC from the human tonsil, the lymph node, and the spleen (secondary lymphoid organs [SLO]) but barely on terminally mature bone marrow PC. IL-21 enhanced Ig secretion by isolated SLO PC but not bone marrow PC. Tonsillar T follicular helper (Tfh) lymphocytes are known to secrete IL-21. Purified Tfh cells induced a marked increase of Ig production by tonsillar PC, and this effect was impaired when endogenous IL-21 production was blocked. IL-21 provoked a rapid and transient phosphorylation of STAT3 in tonsillar PC. Tfh cells or exogenous IL-21 reduce tonsillar PC apoptosis and increases PC recovery but does not modify their nonproliferating status. These results suggest that IL-21 derived from Tfh cells acts as a survival factor for SLO PC in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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B-Lymphocytes / immunology
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Bone Marrow / immunology
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Bone Marrow / metabolism
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Bone Marrow Cells / immunology
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Cells, Cultured
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Humans
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Immunoglobulins / biosynthesis
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Interleukin-21
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Interleukins / immunology
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Interleukins / metabolism*
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymphocyte Activation
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Palatine Tonsil / cytology
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Palatine Tonsil / immunology
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Palatine Tonsil / metabolism
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Phosphorylation
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Plasma Cells / cytology
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Plasma Cells / immunology*
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Plasma Cells / metabolism
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Receptors, Interleukin-21 / immunology
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Receptors, Interleukin-21 / metabolism
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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Immunoglobulins
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Interleukins
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Receptors, Interleukin-21
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STAT3 Transcription Factor
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STAT3 protein, human
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Interleukin-21