title: G-CSF-stimulated neutrophils are a prominent source of functional BLyS.
abstract: B lymphocyte stimulator (BLyS) is a novel member of the TNF ligand superfamily that is important in B cell maturation and survival. We demonstrate that human neutrophils, after incubation with G-CSF or, less efficiently, IFN gamma, express high levels of BLyS mRNA and release elevated amounts of biologically active BLyS. In contrast, surface expression of the membrane-bound BLyS was not detected in activated neutrophils. Indeed, in neutrophils, uniquely among other myeloid cells, soluble BLyS is processed intracellularly by a furin-type convertase. Worthy of note, the absolute capacity of G-CSF-stimulated neutrophils to release BLyS was similar to that of activated monocytes or dendritic cells, suggesting that neutrophils might represent an important source of BLyS. In this regard, we show that BLyS serum levels as well as neutrophil-associated BLyS are significantly enhanced after in vivo administration of G-CSF in patients. In addition, serum obtained from two of these patients induced a remarkable accumulation of neutrophil-associated BLyS in vitro. This effect was neutralized by anti-G-CSF antibodies, indicating that G-CSF, present in the serum, stimulated neutrophils to produce BLyS. Collectively, our findings suggest that neutrophils, through the production of BLyS, might play an unsuspected role in the regulation of B cell homeostasis.
authors.affiliation: Department of Pathology, University of Verona, 37134 Verona, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Scapini
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Nardelli
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Nadali
authors.forename: Federica
authors.initials: F
authors.lastname: Calzetti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.forename: Marco A
authors.initials: MA
authors.lastname: Cassatella
mesh_terms: D053264:B-Cell Activating Factor; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D009500:Neutralization Tests; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D053264:B-Cell Activating Factor; D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor