Pifer Jeannette, Stephan Robert P, Lill-Elghanian Deborah A, Le Phong T, Witte Pamela L
Immunology and Aging Program, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA.
Mech Ageing Dev. 2003 Feb;124(2):207-18. doi: 10.1016/s0047-6374(02)00141-0.
Bone marrow stromal cells are potent providers of stimuli that induce proliferation of B-cell precursors. We proposed that stromal cells play a role in protecting B-lineage cells from corticosteroid-induced apoptosis. We found that stromal cells protected B-cell precursors from dexamethasone-induced apoptosis, but this did not strictly correlate with interleukin-7 (IL-7) production. To determine if stromal-derived factors were involved in protection of B-cell precursors from apoptosis, we examined the activity of three lymphopoietic growth factors: IL-7, stem cell factor (SCF), and insulin-like growth factor-1 (IGF-1). Either IL-7 or IGF-1 alone protected B-cell precursors from dexamethasone-induced apoptosis. The combined activities of IGF-1 and IL-7 were additive rather than synergistic. SCF did not protect B-cell precursors from apoptosis. Aging altered the ability of B-cell precursors to respond to protective stimuli induced by IL-7 and IGF-1. Precursors from aged animals were deficient in ability to modulate expression of apoptosis regulatory genes Bax, Bcl-2, and Bcl-x in comparison to B-cell precursors from young animals. Taken together, these results suggest that stromal cells can protect B-lineage precursors from a corticosteroid-induced apoptotic signal, protection is mediated by stromal-derived cytokines, and aging decreases the ability of B-cell precursors to respond efficiently to protective stimuli.
骨髓基质细胞是诱导B细胞前体增殖的有效刺激物提供者。我们提出基质细胞在保护B系细胞免受皮质类固醇诱导的凋亡中发挥作用。我们发现基质细胞可保护B细胞前体免受地塞米松诱导的凋亡，但这与白细胞介素-7（IL-7）的产生并无严格关联。为了确定基质衍生因子是否参与保护B细胞前体免受凋亡，我们检测了三种淋巴细胞生成生长因子的活性：IL-7、干细胞因子（SCF）和胰岛素样生长因子-1（IGF-1）。单独的IL-7或IGF-1均可保护B细胞前体免受地塞米松诱导的凋亡。IGF-1和IL-7的联合活性是相加的而非协同的。SCF不能保护B细胞前体免受凋亡。衰老改变了B细胞前体对IL-7和IGF-1诱导的保护刺激的反应能力。与年轻动物的B细胞前体相比，老年动物的前体在调节凋亡调节基因Bax、Bcl-2和Bcl-x表达的能力上存在缺陷。综上所述，这些结果表明基质细胞可保护B系前体免受皮质类固醇诱导的凋亡信号影响，这种保护由基质衍生的细胞因子介导，且衰老会降低B细胞前体有效响应保护刺激的能力。
