Defrance T, Vanbervliet B, Aubry J P, Banchereau J
UNICET, Laboratory for Immunological Research, Dardilly, France.
J Exp Med. 1988 Oct 1;168(4):1321-37. doi: 10.1084/jem.168.4.1321.
The combined effect of IL-4 and IL-2 on proliferation of anti-IgM antibody or Staphylococcus aureus strain Cowan I (SAC)-preactivated B cells was investigated. It was observed that in most cases, rIL-2 used at optimal concentration induced higher levels of tritiated thymidine ([3H]TdR) uptake than rIL-4 used at optimal concentration. When rIL-4 and rIL-2 were added together, it was repeatedly found that B cell proliferation induced by rIL-2 was significantly reduced and was, in most cases, comparable with the proliferation induced by rIL-4 alone. Cell cycle studies demonstrated that rIL-4 significantly reduced the number of cells entering S and G2/M phases of the cell cycle upon rIL-2 stimulation. B cell blasts preincubated for 24 or 48 h with rIL-4 displayed a reduced proliferation in response to rIL-2. In contrast, preculture of resting B cells with rIL-4 did not impair their subsequent proliferation in response to rIL-2 plus insolubilized anti-IgM antibody. This suggests that rIL-4 can only exert its inhibitory effect once B cells have received an activation signal. The differentiative activity of rIL-2 measured on B cell blasts preactivated for 2 d with SAC was not altered by rIL-4, which suggests that rIL-4 did not exert its inhibitory activity on rIL-2-induced B cell proliferation by enhancing rIL-2-mediated differentiation. Delayed addition of a neutralizing anti-IL-4 antiserum demonstrated that a period of contact of at least 24 h between IL-4 and B cell blasts was necessary for the development of the antagonistic effect of IL-4 on IL-2-mediated growth of activated B cells. These data demonstrate that IL-4 antagonizes the B cell growth-promoting effect of IL-2 without affecting the differentiation of preactivated B cells in response to IL-2.
研究了白细胞介素-4（IL-4）和白细胞介素-2（IL-2）对抗IgM抗体或考恩I型金黄色葡萄球菌（SAC）预激活的B细胞增殖的联合作用。观察到，在大多数情况下，以最佳浓度使用的重组IL-2（rIL-2）诱导的氚化胸腺嘧啶核苷（[3H]TdR）摄取水平高于以最佳浓度使用的重组IL-4（rIL-4）。当将rIL-4和rIL-2一起添加时，反复发现rIL-2诱导的B细胞增殖显著降低，并且在大多数情况下，与单独由rIL-4诱导的增殖相当。细胞周期研究表明，rIL-4在rIL-2刺激后显著减少进入细胞周期S期和G2/M期的细胞数量。用rIL-4预孵育24或48小时的B细胞母细胞对rIL-2的反应显示增殖减少。相反，用rIL-4对静息B细胞进行预培养并不损害其随后对rIL-2加不溶性抗IgM抗体的增殖反应。这表明rIL-4只有在B细胞接收到激活信号后才能发挥其抑制作用。用SAC预激活2天的B细胞母细胞上测量的rIL-2的分化活性未被rIL-4改变，这表明rIL-4不是通过增强rIL-2介导的分化来对rIL-2诱导的B细胞增殖发挥其抑制活性。延迟添加中和抗IL-4抗血清表明，IL-4与B细胞母细胞之间至少需要24小时的接触期，才能产生IL-4对IL-2介导的活化B细胞生长的拮抗作用。这些数据表明，IL-4拮抗IL-2促进B细胞生长的作用，而不影响预激活的B细胞对IL-2的分化。
