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Research article2012Peer reviewed

B lymphocytes enhance interferon-a production by plasmacytoid dendritic cells

Berggren, Olof; Hagberg, Niklas; Weber, Gert; Alm, Gunnar; Rönnblom, Lars; Eloranta, Maija-Leena

Abstract

Objective The type I interferon (IFN) system and B cells are activated in many autoimmune diseases, such as systemic lupus erythematosus (SLE). The IFNa 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 IFNa 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. IFNa, several other cytokines, and PDC- or B cellassociated surface molecules were analyzed using immunoassays or flow cytometry. Results B cells enhanced IFNa 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 ICinduced IFNa production by 80% but had no effect on IFNa production when ODN 2216 was used as an inducer. Supernatants from ODN 2216stimulated B cells promoted IFNa production by PDCs, while supernatants from RNA-containing ICstimulated 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 PDCB 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.

Published in

Arthritis and Rheumatism
2012, Volume: 64, number: 10, pages: 3409-3419 Publisher: WILEY-BLACKWELL

    UKÄ Subject classification

    Other Veterinary Science

    Publication identifier

    DOI: https://doi.org/10.1002/art.34599

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/45081