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  • Title: B lymphocytes enhance interferon-α production by plasmacytoid dendritic cells.
    Author: Berggren O, Hagberg N, Weber G, Alm GV, Rönnblom L, Eloranta ML.
    Journal: Arthritis Rheum; 2012 Oct; 64(10):3409-19. PubMed ID: 22736048.
    Abstract:
    OBJECTIVE: The type I interferon (IFN) system and B cells are activated in many autoimmune diseases, such as systemic lupus erythematosus (SLE). The IFNα produced by plasmacytoid dendritic cells (PDCs) stimulates several B cell functions, including autoantibody production. However, not much is known about how B cells influence PDC function. The aim of this study was to investigate the regulatory effect of B cells on IFNα production by PDCs. METHODS: PDCs and B cells isolated from peripheral blood mononuclear cells from healthy blood donors were stimulated with RNA-containing immune complexes (ICs) consisting of U1 small nuclear RNP and SLE IgG, herpes simplex virus, or oligonucleotide (ODN) 2216, alone or in cocultures. IFNα, several other cytokines, and PDC- or B cell-associated surface molecules were analyzed using immunoassays or flow cytometry. RESULTS: B cells enhanced IFNα production by PDCs up to 47-fold, and the effect was most pronounced for PDCs stimulated with RNA-containing ICs. Anti-CD31 antibody reduced RNA-containing IC-induced IFNα production by 80% but had no effect on IFNα production when ODN 2216 was used as an inducer. Supernatants from ODN 2216-stimulated B cells promoted IFNα production by PDCs, while supernatants from RNA-containing IC-stimulated B cells did not. CONCLUSION: Our results showed that a novel function of B cells is enhancement of type I IFN production by PDCs. Because B cells are activated by type I IFN, this PDC-B cell cross-talk might be of fundamental importance in the etiopathogenesis of SLE and contribute to long-term immune activation in SLE and other systemic rheumatic diseases.
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