Abstract
The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN-dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we demonstrate that SLE-DCs can efficiently stimulate naive and memory B cells to differentiate into IgG- and IgA-plasmablasts (PBs) resembling those found in the blood of SLE patients. SLE-DC-mediated IgG-PB differentiation is dependent on B cell-activating factor (BAFF) and IL-10, whereas IgA-PB differentiation is dependent on a proliferation-inducing ligand (APRIL). Importantly, SLE-DCs express CD138 and trans-present CD138-bound APRIL to B cells, leading to the induction of IgA switching and PB differentiation in an IFN-α-independent manner. We further found that this mechanism of providing B cell help is relevant in vivo, as CD138-bound APRIL is expressed on blood monocytes from active SLE patients. Collectively, our study suggests that a direct myeloid DC-B cell interplay might contribute to the pathogenesis of SLE.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Autoantibodies / immunology
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Autoantibodies / pharmacology
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B-Cell Activating Factor / immunology
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B-Cell Activating Factor / 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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Cells, Cultured
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Child
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Child, Preschool
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Coculture Techniques
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Female
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Flow Cytometry
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Humans
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Immunoglobulin A / immunology
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Immunoglobulin G / immunology
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Infant
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Interleukin-10 / immunology
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Interleukin-10 / metabolism
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Lupus Erythematosus, Systemic / blood
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Lupus Erythematosus, Systemic / immunology*
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Male
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Monocytes / drug effects
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Monocytes / immunology*
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Monocytes / metabolism
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Plasma Cells / drug effects
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Plasma Cells / immunology*
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Plasma Cells / metabolism
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Serum / immunology
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Syndecan-1 / immunology
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Syndecan-1 / metabolism
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Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology
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Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism
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Young Adult
Substances
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Autoantibodies
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B-Cell Activating Factor
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Immunoglobulin A
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Immunoglobulin G
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Syndecan-1
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Tumor Necrosis Factor Ligand Superfamily Member 13
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Interleukin-10