Garvy B A, Riley R L
Department of Microbiology and Immunology, University of Miami School of Medicine, FL 33101.
Immunology. 1994 Mar;81(3):381-8.
These studies investigated the mechanism by which interferon-gamma (IFN-gamma) inhibits the interleukin-7 (IL-7)-dependent proliferation of BALB/c bone marrow B-cell precursors in vitro. Low concentrations (1 U/ml) of recombinant murine IFN-gamma (rmIFN-gamma) caused a approximately 80% suppression of IL-7 colony-forming units (CFU) formation in semi-solid media, in part through a direct affect on isolated B220+ pre-B cells. IFN-gamma did not induce apoptosis in small resting pre-B cells in BALB/c bone marrow. There was no difference in the proportion of apoptotic B220+ pre-B cells in IFN-gamma-treated cultures compared to cultures treated with IL-7 alone. However, IL-7-responsive pre-B cells generated from bone marrow had a 30-50% loss in cells in S+G2/M phases of the cell cycle and an increase of up to twice as many in apoptotic cells within 48 hr of exposure to IFN-gamma. Notably, expression of the tyrosine phosphatase B220 was increased in the IFN-gamma-treated pre-B cells. Interestingly, although there was no substantial change in IL-7 receptor mRNA expression upon IFN-gamma treatment, a small decrease in binding of biotinylated IL-7 to IFN-gamma-treated pre-B cells was observed. These results suggest that IFN-gamma inhibits IL-7 responsiveness in pre-B cells, resulting in a subtle down-regulation of IL-7 binding, inhibition of proliferation and, ultimately, apoptosis.
这些研究调查了γ干扰素（IFN-γ）在体外抑制白细胞介素-7（IL-7）依赖的BALB/c骨髓B细胞前体增殖的机制。低浓度（1 U/ml）的重组鼠γ干扰素（rmIFN-γ）在半固体培养基中使IL-7集落形成单位（CFU）的形成受到约80%的抑制，部分是通过对分离出的B220+前B细胞的直接作用。IFN-γ并未诱导BALB/c骨髓中静止的小前B细胞凋亡。与仅用IL-7处理的培养物相比，IFN-γ处理的培养物中凋亡的B220+前B细胞比例没有差异。然而，骨髓产生的对IL-7有反应的前B细胞在接触IFN-γ后48小时内，细胞周期S+G2/M期的细胞损失30 - 50%，凋亡细胞增加多达两倍。值得注意的是，IFN-γ处理的前B细胞中酪氨酸磷酸酶B220的表达增加。有趣的是，尽管IFN-γ处理后IL-7受体mRNA表达没有实质性变化，但观察到生物素化的IL-7与IFN-γ处理的前B细胞的结合略有减少。这些结果表明，IFN-γ抑制前B细胞对IL-7的反应性，导致IL-7结合的轻微下调、增殖抑制，并最终导致细胞凋亡。
