title: B lymphocyte stimulator regulates adaptive immune responses by directly promoting dendritic cell maturation.
abstract: B lymphocyte stimulator (BLyS) is a well-known direct costimulator of adaptive immune cells, particularly B lineage cells. However, we have reported recently that BLyS is also able to activate monocytes. Other innate immune cells, such as dendritic cells (DCs), play a key role in the initiation of adaptive immune responses and the purpose of the current study was to assess whether there is a direct role for BLyS in modulating human DC functions. In this study, we show that BLyS induces DC activation and maturation. Thus, BLyS strongly induced up-regulation of surface costimulatory molecule expression and secretion of specific cytokines and chemokines in DCs. BLyS-stimulated DCs (BLyS-DCs) were also able to augment allogeneic CD4 T cell proliferation to a greater extent than control DCs. BLyS-DCs secreted elevated levels of the major Th1-polarizing cytokine, IL-12p70, and they promoted naive CD4 T cell differentiation into Th1 T cells. Regarding BLyS receptor expression, DCs primarily express cytoplasmic transmembrane activator and CAML interactor; however, low levels of cell surface transmembrane activator and CAML interactor are expressed as well. Collectively, our data suggest that BLyS may modulate adaptive immune cells indirectly by inducing DC maturation.
authors.affiliation: Department of Immunology, College of Medicine, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sook Kyung
authors.initials: SK
authors.lastname: Chang
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Mihalcik
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
mesh_terms: D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007110:Immunity, Active; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D040081:Protein Array Analysis; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D016207:Cytokines; D018664:Interleukin-12