Yoshimoto T, Nakanishi K, Matsui K, Hirose S, Hiroishi K, Tanaka T, Hada T, Hamaoka T, Higashino K
Third Department of Internal Medicine, Hyogo College of Medicine, Japan.
J Immunol. 1990 Jan 1;144(1):183-90.
Both IL-4 and IL-5 demonstrate B cell growth activity. IL-5 can render a cloned neoplastic B cell line, BCL1-CL-3 cells, responsive to IL-2, whereas IL-4 has no such activity. The response to IL-5 and IL-2 proceeds in two phases: the first phase which clearly depends upon IL-5 is the obvious increase in number of high affinity IL-2R (3.1-fold) with modest increase of low affinity IL-2R (1.2-fold) and gain of the ability of facilitated IL-2-binding and internalization of IL-2, and the second phase which is induced by IL-2 in the IL-5-stimulated CL-3 cells comprises the striking increase of low affinity IL-2R (8.5-fold). Kinetic study has revealed that high affinity IL-2R expressed on CL-3 cells begins to increase at 6 h and reaches to maximum at 12 h after stimulation with IL-5 or IL-5 plus IL-2, whereas low affinity IL-2R expression increases at 18 h and becomes maximal at 24 h after stimulation of CL-3 cells with IL-5 and IL-2. However, in the presence of IL-4, IL-5 cannot induce an increase in number of high affinity IL-2R on CL-3 cells. Thus, CL-3 cells stimulated with the mixture of IL-5 and IL-4 cannot respond to IL-2, and fail to show up-regulated expression of low affinity IL-2R. IL-4 also has a capacity to modestly interfere with the action of IL-2 to up-regulate low affinity IL-2R expression on IL-5-pretreated CL-3 cells. Thus, this monoclonal B cell system provides an excellent model system to define the roles of IL-5 and IL-4 involved in the B cell differentiation and to characterize the properties of B cells competent to IL-2 stimulation and the signal transduction mechanism which operates through IL-2/IL-2R system.
白细胞介素-4(IL-4)和白细胞介素-5(IL-5)均表现出B细胞生长活性。IL-5可使克隆的肿瘤性B细胞系BCL1-CL-3细胞对IL-2产生反应,而IL-4则无此活性。对IL-5和IL-2的反应分两个阶段进行:第一阶段明显依赖于IL-5,表现为高亲和力IL-2受体数量明显增加(3.1倍),低亲和力IL-2受体略有增加(1.2倍),并获得促进IL-2结合及IL-2内化的能力;第二阶段由IL-2在IL-5刺激的CL-3细胞中诱导产生,表现为低亲和力IL-2受体显著增加(8.5倍)。动力学研究表明,CL-3细胞上表达的高亲和力IL-2受体在用IL-5或IL-5加IL-2刺激后6小时开始增加,12小时达到最大值,而在用IL-5和IL-2刺激CL-3细胞后,低亲和力IL-2受体表达在18小时增加,24小时达到最大值。然而,在有IL-4存在的情况下,IL-5不能诱导CL-3细胞上高亲和力IL-2受体数量增加。因此,用IL-5和IL-4混合物刺激的CL-3细胞不能对IL-2产生反应,也未表现出低亲和力IL-2受体表达上调。IL-4也有适度干扰IL-2作用的能力,使其不能上调IL-5预处理的CL-3细胞上低亲和力IL-2受体的表达。因此,这个单克隆B细胞系统为确定IL-5和IL-4在B细胞分化中的作用、表征对IL-2刺激有反应的B细胞特性以及通过IL-2/IL-2受体系统起作用的信号转导机制提供了一个极好的模型系统。