title: Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice.
abstract: The mechanisms that mediate the shift from lymphopoiesis to myelopoiesis in response to infectious stress are largely unknown. We show that treatment with granulocyte colony-stimulating factor (G-CSF), which is often induced during infection, results in marked suppression of B lymphopoiesis at multiple stages of B-cell development. Mesenchymal-lineage stromal cells in the bone marrow, including CXCL12-abundant reticular (CAR) cells and osteoblasts, constitutively support B lymphopoiesis through the production of multiple B trophic factors. G-CSF acting through a monocytic cell intermediate reprograms these stromal cells, altering their capacity to support B lymphopoiesis. G-CSF treatment is associated with an expansion of CAR cells and a shift toward osteogenic lineage commitment. It markedly suppresses the production of multiple B-cell trophic factors by CAR cells and osteoblasts, including CXCL12, kit ligand, interleukin-6, interleukin-7, and insulin-like growth factor-1. Targeting bone marrow stromal cells is one mechanism by which inflammatory cytokines such as G-CSF actively suppress lymphopoiesis.
authors: Department of Medicine and.
authors: Ryan B
authors: RB
authors: Day
authors: Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO;
authors: Deepta
authors: D
authors: Bhattacharya
authors: Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan; and Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Tokyo, Japan.
authors: Takashi
authors: T
authors: Nagasawa
authors: Department of Medicine and.
authors: Daniel C
authors: DC
authors: Link
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016130:Immunophenotyping; D038041:Lymphopoiesis / Q000187:drug effects* / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D016179:Granulocyte Colony-Stimulating Factor