Day Ryan B, Bhattacharya Deepta, Nagasawa Takashi, Link Daniel C
Department of Medicine and.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO;
Blood. 2015 May 14;125(20):3114-7. doi: 10.1182/blood-2015-02-629444. Epub 2015 Mar 26.
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.
在感染应激反应中，介导淋巴细胞生成向髓细胞生成转变的机制在很大程度上尚不清楚。我们发现，感染期间常被诱导产生的粒细胞集落刺激因子（G-CSF）治疗，会在B细胞发育的多个阶段显著抑制B淋巴细胞生成。骨髓中的间充质谱系基质细胞，包括富含CXCL12的网状（CAR）细胞和成骨细胞，通过产生多种B细胞营养因子持续支持B淋巴细胞生成。G-CSF通过单核细胞中间体发挥作用，对这些基质细胞进行重编程，改变它们支持B淋巴细胞生成的能力。G-CSF治疗与CAR细胞的扩增以及向成骨谱系定向分化的转变有关。它显著抑制CAR细胞和成骨细胞产生多种B细胞营养因子，包括CXCL12、kit配体、白细胞介素-6、白细胞介素-7和胰岛素样生长因子-1。靶向骨髓基质细胞是G-CSF等炎性细胞因子积极抑制淋巴细胞生成的一种机制。
