title: Production of the plasma-cell survival factor a proliferation-inducing ligand (APRIL) peaks in myeloid precursor cells from human bone marrow.
abstract: The bone marrow (BM) is an organ extremely efficient in mediating long-term survival of plasma cells (PCs), ensuring an immune humoral memory. This implies that the BM must provide continuously key PC survival factors. Our results show that the BM is an organ constitutively rich in a proliferation-inducing ligand (APRIL), a member of the tumor necrosis factor superfamily implicated in PC survival. APRIL production is induced during hematopoiesis in myeloid cells by non-lineage-committing factors such as stem cell factor, thrombopoietin, IL-3, and FMS-like tyrosine kinase 3 ligand. Notably, APRIL production, both in the human and mouse systems, peaks in myeloid precursor cells, before dropping in fully mature granulocytes. Myeloid cells secrete APRIL that circulates freely in BM plasma to act on PCs, usually at distance from APRIL production sites. Selective APRIL in vivo antagonism and in vitro coculture experiments further demonstrated that myeloid precursor cells mediates PC survival in an APRIL-dependent manner Thus, APRIL production by myeloid precursor cells shows that the 2 main BM functions, hematopoiesis and long-term PC survival, are linked. Such constitutive and high APRIL production may explain why BM mediates long-term PC survival.
authors.affiliation: Division of Hematology, University Hospitals, Geneva, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Matthes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dunand-Sauthier
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Santiago-Raber
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Krause
authors.forename: Olivier
authors.initials: O
authors.lastname: Donze
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.forename: Tomas
authors.initials: T
authors.lastname: McKee
authors.forename: Bertrand
authors.initials: B
authors.lastname: Huard
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D055786:Gene Knockout Techniques; D006801:Humans; D019891:Leukopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053300:Tumor Necrosis Factor Ligand Superfamily Member 13