A role for BLyS in the activation of innate immune cells.
B-lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) ligand superfamily. Although BLyS costimulates adaptive immune cells, the ability of BLyS to stimulate innate immune cells has not been described. Here, we show that BLyS strongly induces human monocyte survival, and activation as measured by proinflammatory cytokine secretion and up-regulation of costimulatory molecule expression. In addition, monocytes cultured with BLyS differentiated into macrophage-like cells. Regarding BLyS receptor(s) expression, freshly isolated monocytes bound low levels of exogenous BLyS and expressed primarily intracellular TACI, and cell surface TACI levels increased following monocyte activation. Of interest, bone marrow monocytes from some multiple myeloma patients expressed significant levels of cell surface TACI at isolation. Our findings indicate that BLyS plays a role in activating innate immune cells. Moreover, this study may explain more clearly why high BLyS production is often correlated with certain inflammatory autoimmune diseases and B-lymphocyte malignancies.
Chang
Sook Kyung
SK
Department of Immunology, Guggenheim 4, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Arendt
Bonnie K
BK
Darce
Jaime R
JR
Wu
Xiaosheng
X
Jelinek
Diane F
DF
D017209:Apoptosis / Q000187:drug effects; D053264:B-Cell Activating Factor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009101:Multiple Myeloma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D053264:B-Cell Activating Factor; D016207:Cytokines; D008565:Membrane Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha