title: Synthesis and release of B-lymphocyte stimulator from myeloid cells.
abstract: B-lymphocyte stimulator (BLyS) is a recently identified novel member of the tumor necrosis factor ligand superfamily shown to exist in a membrane-bound and soluble form. BLyS was found to be specifically expressed on cells of myeloid lineage and to selectively stimulate B-lymphocyte proliferation and immunoglobulin production. The expression of a cytokine involved in potentiation of humoral immune responses, such as BLyS, is expected to be strictly controlled. The goal of the present study was to examine regulation of BLyS levels in monocytic cells in response to cytokines and during their differentiation to macrophages and dendritic cells. The presence of BLyS on the cell surface and in the culture medium of both normal blood monocytes and on tumor cells of myelomonocytic origin was demonstrated. BLyS gene expression and levels of membrane-associated and soluble BLyS were found to be regulated by cytokines, in particular interferon (IFN)-gamma and to a lesser extent interleukin-10 (IL-10). The expression of BLyS on monocyte membranes was retained following differentiation into macrophages, but detection on the surface of monocyte-derived dendritic cells required stimulation with IFN-gamma. Both IFN-gamma and IL-10 enhanced the release of soluble BLyS that was active in B-cell proliferation assays. Cells transfected with BLyS complementary DNA mutated in a predicted cleavage site failed to release BLyS into the culture medium, thereby suggesting that soluble BLyS was derived from the membrane form. These results provide further support for an important role for BLyS expressed in myeloid cells in B-cell expansion and antibody responses.
authors.affiliation: Human Genome Sciences, Inc, Rockville, MD 20850, USA. bernardetta_nardelli@hgsi.com
authors.forename: B
authors.initials: B
authors.lastname: Nardelli
authors.forename: O
authors.initials: O
authors.lastname: Belvedere
authors.forename: V
authors.initials: V
authors.lastname: Roschke
authors.forename: P A
authors.initials: PA
authors.lastname: Moore
authors.forename: H S
authors.initials: HS
authors.lastname: Olsen
authors.forename: T S
authors.initials: TS
authors.lastname: Migone
authors.forename: S
authors.initials: S
authors.lastname: Sosnovtseva
authors.forename: J A
authors.initials: JA
authors.lastname: Carrell
authors.forename: P
authors.initials: P
authors.lastname: Feng
authors.forename: J G
authors.initials: JG
authors.lastname: Giri
authors.forename: D M
authors.initials: DM
authors.lastname: Hilbert
mesh_terms: D000906:Antibodies / Q000378:metabolism; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000737:chemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012995:Solubility; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D053264:B-Cell Activating Factor; D016207:Cytokines; D008565:Membrane Proteins; D012333:RNA, Messenger; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D010447:Peptide Hydrolases