Kabelitz D, Pfeffer K, von Steldern D, Bartmann P, Brudler O, Nerl C, Wagner H
J Immunol. 1985 Oct;135(4):2876-81.
Recent evidence indicates that interleukin 2 (IL 2), formerly thought to serve as growth factor exclusively for activated T cells, is directly involved in human B cell differentiation. We have investigated the role of IL 2 and IL 2 receptors (as defined by monoclonal anti-Tac antibody) in the phorbol ester-induced in vitro maturation of leukemic B cells from patients with chronic lymphocytic leukemia (CLL). Peripheral blood lymphocytes from B cells from CLL patients with high (greater than 10(5)/microliters) white blood cell counts were depleted of residual T lymphocytes and low-density cells (primarily macrophages) by consecutive steps of E rosetting, complement-mediated lysis of OKT3+ and OKT4+ cells, and Percoll density gradient centrifugation. No OKT3+ T cells were detectable in these cell populations before or after culture. When incubated for 3 days with phorbol ester plus recombinant human IL 2 (rIL 2), 12 to 57% of highly purified B cells from four of five tested patients expressed Tac antigen. Both phorbol ester and rIL 2 were required for maximal Tac antigen expression. Functional studies revealed that phorbol ester-activated (but not resting) CLL B cells responded to rIL 2 with [3H]thymidine incorporation and with enhanced secretion of IgM. Tac+ B cells were isolated in two cases on a fluorescence-activated cell sorter. In one patient, stimulation of Tac+ B cells with rIL 2 resulted in enhanced [3H]thymidine incorporation but no change in IgM secretion, as compared with Tac- B cells; in the second patient, stimulation of Tac+ B cells with rIL 2 did not result in [3H]thymidine uptake, but did result in significant IgM secretion. These findings indicate that certain leukemic B lymphocytes can be induced to express IL 2 receptors and respond to IL 2. The use of resting clonal B cell populations arrested at distinct stages of differentiation may help to better define the stage(s) at which IL 2 acts directly on B cells to induce proliferation and/or terminal differentiation.
最近的证据表明，白细胞介素2（IL-2），以前被认为仅是活化T细胞的生长因子，实际上直接参与人类B细胞的分化。我们研究了IL-2和IL-2受体（由单克隆抗Tac抗体定义）在佛波酯诱导的慢性淋巴细胞白血病（CLL）患者白血病B细胞体外成熟中的作用。通过连续的E花环形成、OKT3 +和OKT4 +细胞的补体介导裂解以及Percoll密度梯度离心步骤，去除高白细胞计数（大于10⁵/微升）的CLL患者B细胞外周血淋巴细胞中的残余T淋巴细胞和低密度细胞（主要是巨噬细胞）。在培养前后，这些细胞群体中均未检测到OKT3 + T细胞。当与佛波酯加重组人IL-2（rIL-2）一起孵育3天时，五名受试患者中有四名的高度纯化B细胞中有12%至57%表达Tac抗原。最大程度的Tac抗原表达需要佛波酯和rIL-2两者。功能研究表明，佛波酯激活的（而非静止的）CLL B细胞对rIL-2有反应，表现为[³H]胸苷掺入增加和IgM分泌增强。在两例中通过荧光激活细胞分选仪分离出Tac + B细胞。在一名患者中，与Tac - B细胞相比，用rIL-2刺激Tac + B细胞导致[³H]胸苷掺入增加，但IgM分泌无变化；在第二名患者中，用rIL-2刺激Tac + B细胞未导致[³H]胸苷摄取，但确实导致显著的IgM分泌。这些发现表明，某些白血病B淋巴细胞可被诱导表达IL-2受体并对IL-2作出反应。使用停滞在不同分化阶段的静止克隆B细胞群体可能有助于更好地确定IL-2直接作用于B细胞以诱导增殖和/或终末分化的阶段。
