Chen X, Liu W, Ambrosino C, Ruocco M R, Poli V, Romani L, Quinto I, Barbieri S, Holmes K L, Venuta S, Scala G
Dipartimento di Medicina Sperimentale e Clinica, Università di Reggio Calabria, Catanzaro, Italy.
Blood. 1997 Jul 1;90(1):156-64.
CAAT/enhancer binding proteins (C/EBP) are a family of transcription factors that mediates adipocyte differentiation and the regulation of genes expressed in immune responses and inflammation, such as interleukin-6 (IL-6), IL-8, and granulocyte colony-stimulating factor (G-CSF). We investigated the role of C/EBPbeta (NF-IL6) in the generation of bone marrow B lymphocytes by taking advantage of C/EBPbeta-/- mice. We found that the expansion of bone marrow (BM) B lymphocytes was impaired in long-term lymphoid cultures from C/EBPbeta-/- mice. Consistent with this finding, the number of BM B cells was decreased in C/EBPbeta-/- mice. Both the levels of IL-7 gene expression and bioactive IL-7 from BM stromal cells were decreased in C/EBPbeta-/- mice. Furthermore, the proliferative responsiveness of BM B-cell precursors to IL-7 was also reduced as compared to wild-type mice, indicating that C/EBPbeta is required for the generation of BM B cells induced by IL-7. Accordingly, IL-7 stimulates the C/EBPbeta DNA-binding activity of normal BM pre-B lymphocytes as well as of 70Z/3 pre-B cells. These results point to C/EBPbeta as a critical signaling molecule in BM B lymphopoiesis.
CAAT/增强子结合蛋白（C/EBP）是一类转录因子家族，介导脂肪细胞分化以及免疫应答和炎症中表达的基因调控，如白细胞介素-6（IL-6）、IL-8和粒细胞集落刺激因子（G-CSF）。我们利用C/EBPβ基因敲除小鼠研究了C/EBPβ（NF-IL6）在骨髓B淋巴细胞生成中的作用。我们发现，来自C/EBPβ基因敲除小鼠的长期淋巴细胞培养中，骨髓（BM）B淋巴细胞的扩增受到损害。与此发现一致，C/EBPβ基因敲除小鼠的BM B细胞数量减少。C/EBPβ基因敲除小鼠中，BM基质细胞的IL-7基因表达水平和生物活性IL-7均降低。此外，与野生型小鼠相比，BM B细胞前体对IL-7的增殖反应性也降低，表明C/EBPβ是IL-7诱导的BM B细胞生成所必需的。因此，IL-7可刺激正常BM前B淋巴细胞以及70Z/3前B细胞的C/EBPβ DNA结合活性。这些结果表明C/EBPβ是BM B淋巴细胞生成中的关键信号分子。
