Ryan D H, Nuccie B L, Ritterman I, Liesveld J L, Abboud C N
Department of Pathology, University of Rochester Medical Center, NY 14642.
J Immunol. 1994 Jun 1;152(11):5250-8.
An in vitro culture system in which bone marrow-derived fibroblast-like cells support the growth of TdT+ colonies derived from CD34+/CD10- human bone marrow progenitor cells has recently been described. The regulatory role of cytokines during early B lineage commitment was investigated using this culture system. Expression of IL-7, a cytokine that induces proliferation of B cell precursors, was detectable in the adherent layer by PCR and bioassay. Lymphoid progenitor colonies were inhibited by neutralizing anti-IL-7 Ab, suggesting that IL-7 produced by the adherent layer was required even in the earliest recognizable stages of human B cell lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha inhibited lymphoid progenitor colonies in a dose-dependent fashion. Neutralizing Ab to IL-1 alpha, IL-4, or TNF-alpha did not increase lymphoid progenitor colonies, suggesting that inhibitory concentrations of these cytokines are not constitutively elaborated in the adherent layer. Recombinant Steel factor and IL-6 as well as neutralizing Abs to these cytokines did not significantly affect lymphoid progenitor colonies, arguing against an important role for these cytokines in early human B lymphopoiesis. These results indicate that IL-7 provided by the bone marrow microenvironment is a critical growth factor at the earliest recognizable stages of human lymphopoiesis. IL-1 alpha, IL-4, and TNF-alpha have been shown to indirectly stimulate release of myeloid growth factors. The inhibition of lymphopoiesis by these cytokines suggests a possible mechanism for the observed reciprocal relationship between lymphoid and myeloid supportive bone marrow microenvironments.
最近报道了一种体外培养系统，其中骨髓来源的成纤维细胞样细胞支持源自CD34 + / CD10-人骨髓祖细胞的TdT +集落的生长。使用该培养系统研究了细胞因子在早期B谱系定向过程中的调节作用。通过PCR和生物测定法在贴壁层中可检测到诱导B细胞前体增殖的细胞因子IL-7的表达。中和抗IL-7抗体可抑制淋巴祖细胞集落，这表明即使在人类B细胞淋巴细胞生成的最早可识别阶段，贴壁层产生的IL-7也是必需的。IL-1α、IL-4和TNF-α以剂量依赖性方式抑制淋巴祖细胞集落。针对IL-1α、IL-4或TNF-α的中和抗体不会增加淋巴祖细胞集落，这表明这些细胞因子的抑制浓度在贴壁层中不是组成性产生的。重组Steel因子和IL-6以及针对这些细胞因子的中和抗体对淋巴祖细胞集落没有显著影响，这表明这些细胞因子在早期人类B淋巴细胞生成中没有重要作用。这些结果表明，骨髓微环境提供的IL-7是人类淋巴细胞生成最早可识别阶段的关键生长因子。IL-1α、IL-4和TNF-α已被证明可间接刺激髓系生长因子的释放。这些细胞因子对淋巴细胞生成的抑制作用提示了观察到的淋巴样和髓样支持性骨髓微环境之间相互关系的一种可能机制。
