B lymphocytes enhance interferon-α production by plasmacytoid dendritic cells.
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.


CONCLUSIONS
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.
Uppsala University, Uppsala, Sweden.
Olof
O
Berggren
Niklas
N
Hagberg
Gert
G
Weber
Gunnar V
GV
Alm
Lars
L
Rönnblom
Maija-Leena
ML
Eloranta
D000936:Antigen-Antibody Complex / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D016898:Interferon-alpha