B lymphocytes enhance interferon-α production by plasmacytoid dendritic cells

Arthritis Rheum. 2012 Oct;64(10):3409-19. doi: 10.1002/art.34599.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Complex / metabolism
  • Antigens, CD / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism*
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism*
  • Humans
  • Interferon-alpha / biosynthesis*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / metabolism

Substances

  • Antigen-Antibody Complex
  • Antigens, CD
  • Interferon-alpha