Abstract
Maturation and selection of high-affinity B cell clones in the germinal center (GC) relies on support from T follicular helper (T(FH)) cells. T(FH) cells are characterized by their localization to the B cell follicle and their high expression of the costimulatory molecules ICOS and PD1 and the cytokine IL-21, which promotes immunoglobulin (Ig) class switching and production by B cells. We show that the heterodimeric cytokine IL-27 is critical for the function of T(FH) cells and for normal and pathogenic GC responses. IL-27 signaling to T cells results in the production of IL-21, a known autocrine factor for the maintenance of T(FH) cells, in a STAT3-dependent manner. IL-27 also enhances the survival of activated CD4(+) T cells and the expression of T(FH) cell phenotypic markers. In vivo, expression of the IL-27Rα chain is required to support IL-21 production and T(FH) cell survival in a T cell-intrinsic manner. The production of high-affinity antibodies is reduced, and pristane-elicited autoantibodies and glomerulonephritis are significantly diminished, in Il27ra(-/-) mice. Together, our data show a nonredundant role for IL-27 in the development of T cell-dependent antibody responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Bone Marrow / immunology
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Bone Marrow / metabolism
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Bone Marrow Transplantation
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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Cells, Cultured
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Female
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Flow Cytometry
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Gene Expression / drug effects
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Germinal Center / drug effects
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Germinal Center / immunology*
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Germinal Center / metabolism
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Interleukins / genetics
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Interleukins / immunology*
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Interleukins / metabolism*
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Interleukins / pharmacology
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Lupus Erythematosus, Systemic / chemically induced
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Lupus Erythematosus, Systemic / immunology
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Male
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Mice
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Mice, 129 Strain
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Cytokine / deficiency
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Receptors, Cytokine / genetics
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Receptors, Cytokine / immunology
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Receptors, Interleukin
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / immunology
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T-Lymphocytes, Helper-Inducer / drug effects
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Terpenes
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Transplantation Chimera / immunology
Substances
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Il27 protein, mouse
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Il27ra protein, mouse
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Interleukins
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Receptors, Cytokine
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Receptors, Interleukin
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Terpenes
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pristane
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interleukin-21