title: IFN-α produced by human plasmacytoid dendritic cells enhances T cell-dependent naïve B cell differentiation.
abstract: The development and quality of a humoral immune response are largely influenced by the environment that supports the activation of naïve B cells. Human PDCs, through their unique capacity to produce high levels of IFN-α, have been shown earlier to enhance B cell responses stimulated by selected TLR ligands. In this study, we investigated whether PDCs also promote B cell activation induced by Th cell interactions and BCR ligation. Sorted human naive CD19(+) CD27(-) B cells were activated in vitro with anti-Ig and irradiated CD4(+) T cells. Under these conditions, the presence of supernatants from TLR-stimulated PDCs increased B cell proliferation, the frequency of B cells that differentiated to CD27(high) CD38(high) cells, and secretion of IgM. Similar results were observed when the B cells were activated in the presence of purified IFN-α. In contrast, supernatants from stimulated MDCs did not augment these functions. Also, IFN-α treatment of B cells up-regulated the expression of costimulatory molecule CD86 but not CD40, CD80, MHC class II, or CD25. Although direct IFN-α exposure of T cells suppressed their proliferative capacity, IFN-α treatment of B cells led to a small increase in their capacity to induce superantigen-driven activation of autologous CD4(+) T cells. In summary, PDCs, via their production of IFN-α, may render B cells more responsive to T cell contact, which in turn, facilitates B cell proliferation and differentiation to antibody-producing cells.
authors.affiliation: Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Gujer
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Sandgren
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: William C
authors.initials: WC
authors.lastname: Adams
authors.forename: Christopher
authors.initials: C
authors.lastname: Sundling
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
mesh_terms: D000921:Antibody-Producing Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000378:metabolism*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D007075:Immunoglobulin M; D016898:Interferon-alpha