Touw I, Dorssers L, Löwenberg B
Blood. 1987 Jun;69(6):1667-73.
To determine the growth properties of B cell chronic lymphocytic leukemia (B CLL) and to identify possible abnormalities thereof, we examined the in vitro action of interleukin 2 (IL2) in four patients. Using radiolabeled IL2 and monoclonal antibodies reactive with IL2 membrane receptors we show that CLL cells, after their activation in vitro, express IL2 receptors of a high- as well as a low-affinity type, exactly as has been reported for normal T and B blasts. In three of the four reported cases, CLL proliferation (measured with 3H-thymidine incorporation) depended on the addition of phytohemagglutinin (PHA) to activate the cells and IL2 (optimal concentration, 10 to 100 U IL2/mL). In contrast, the cells of the fourth case of CLL (CLL-4) proliferated in an autonomous fashion, ie, without a need for PHA and IL2 in culture. Specific blocking of the IL2-binding sites with anti-IL2 receptor monoclonal antibodies almost completely inhibited the proliferation of these cells, which indicated that functional IL2 receptors were required for the autonomous proliferation. The demonstration of low concentrations of IL2 activity in the culture medium conditioned by the cells suggests that endogenous IL2 had been responsible for the spontaneous 3H-thymidine uptake by the CLL cells of patient 4. However, we were unable to extract IL2 mRNA from the cells (neither fresh nor after various in vitro incubations) in quantities detectable by Northern blot analysis that would prove that the CLL cells of patient 4 were actively synthesizing IL2 during culture. Thus, individual cases of B CLL are subject to variable growth regulation involving functional IL2 receptors on the cell surface: after activation with PHA the cells respond to exogenous IL2 in a fashion similar to normal B lymphocytes, or the cells are stimulated by endogenous IL2 (or an IL2-like activity) and do not require activation with PHA.
为了确定B细胞慢性淋巴细胞白血病（B - CLL）的生长特性并识别其可能存在的异常，我们检测了4例患者白细胞介素2（IL - 2）的体外作用。通过使用放射性标记的IL - 2和与IL - 2膜受体反应的单克隆抗体，我们发现慢性淋巴细胞白血病细胞在体外激活后，表达高亲和力和低亲和力类型的IL - 2受体，这与正常T和B母细胞的情况完全一致。在所报道的4例病例中的3例中，慢性淋巴细胞白血病细胞的增殖（通过³H - 胸腺嘧啶核苷掺入量来测定）依赖于添加植物血凝素（PHA）来激活细胞以及IL - 2（最佳浓度为10至100 U IL - 2/mL）。相比之下，第4例慢性淋巴细胞白血病（CLL - 4）患者的细胞以自主方式增殖，即在培养中无需PHA和IL - 2。用抗IL - 2受体单克隆抗体特异性阻断IL - 2结合位点几乎完全抑制了这些细胞的增殖，这表明功能性IL - 2受体是自主增殖所必需的。细胞条件培养液中低浓度IL - 2活性的证明表明，内源性IL - 2导致了患者4的慢性淋巴细胞白血病细胞对³H - 胸腺嘧啶核苷的自发摄取。然而，我们无法从细胞中（无论是新鲜细胞还是经过各种体外培养后）提取到通过Northern印迹分析可检测到的足够量的IL - 2 mRNA，以证明患者4的慢性淋巴细胞白血病细胞在培养过程中正在积极合成IL - 2。因此，个别B - CLL病例受到涉及细胞表面功能性IL - 2受体的可变生长调节：用PHA激活后，细胞对外源性IL - 2的反应方式类似于正常B淋巴细胞，或者细胞受到内源性IL - 2（或类似IL - 2的活性物质）刺激，不需要PHA激活。
