Shubinsky G, Schlesinger M, Polliack A, Rabinowitz R
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Leuk Lymphoma. 1997 May;25(5-6):521-30. doi: 10.3109/10428199709039040.
The aim of the present study was to analyze the pathways regulating the expression of CD21 and CD23 B-cell differentiation antigens on human malignant B cells. Exposure of Farage cells, derived from a human B-cell lymphoma, to phorbol 12-myristate 13-acetate (PMA) down-regulated CD21 and CD23 expression, while interleukin 4 (IL4) inhibited the expression of CD21 but augmented CD23 expression. When Farage cells were stained with either anti-CD21 or anti-CD23 monoclonal antibodies (mAb), subsequent exposure to IL4 failed to change the staining of the cells, indicating that IL4 did not affect the turnover of CD21 and CD23 molecules. Inhibition of protein synthesis with cycloheximide (CXM) had no effect on the expression of CD21 molecules, but abrogated their down-regulation by IL4, suggesting that IL4 induced the synthesis of proteins which modify the processing of CD21 molecules. The inhibitory effect of IL4 on the expression of CD21 and its augmentary effect on the expression of CD23 was abrogated by H7 (1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine), an inhibitor of serine protein kinase. Staurosporine, an additional inhibitor of serine kinases also abrogated the effect of IL4 on CD23 expression. H8 (N-(2-[Methylamino]ethyl)-5-isoquinolinesulfonamide), a preferential inhibitor of protein kinases A and G, and genistein, an inhibitor of tyrosine kinases had no effect on IL4-induced modulation of CD21 and CD23 in Farage cells. The exposure of B-chronic lymphocytic leukemia (CLL) cells to PMA reduced the expression of CD21, but increased the expression of CD23. IL4 had no effect on the expression of CD21 on CLL-cells but strongly enhanced the level of CD23. H7, H8 and genistein each abrogated to a different extent the effect of IL4 on the expression of CD23 by CLL-cells. These data indicate that activation of serine/threonine kinases in malignant B cells inhibited the production of CD21 proteins, while different protein kinases appeared to be involved in up- and down-regulation of CD23 in different B lymphocytes.
本研究的目的是分析调节人类恶性B细胞上CD21和CD23 B细胞分化抗原表达的途径。源自人类B细胞淋巴瘤的法拉吉（Farage）细胞暴露于佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）后，CD21和CD23表达下调，而白细胞介素4（IL4）抑制CD21的表达但增强CD23的表达。当用抗CD21或抗CD23单克隆抗体（mAb）对法拉吉细胞进行染色后，随后暴露于IL4未能改变细胞的染色情况，这表明IL4不影响CD21和CD23分子的周转。用环己酰亚胺（CXM）抑制蛋白质合成对CD21分子的表达没有影响，但消除了IL4对其的下调作用，这表明IL4诱导了修饰CD21分子加工过程的蛋白质的合成。丝氨酸蛋白激酶抑制剂H7（1 -（5 - 异喹啉磺酰基）- 2 - 甲基哌嗪）消除了IL4对CD21表达的抑制作用及其对CD23表达的增强作用。另一种丝氨酸激酶抑制剂星形孢菌素也消除了IL4对CD23表达的影响。蛋白激酶A和G的优先抑制剂H8（N -（2 - [甲氨基]乙基）- 5 - 异喹啉磺酰胺）以及酪氨酸激酶抑制剂染料木黄酮对IL4诱导的法拉吉细胞中CD21和CD23的调节没有影响。B细胞慢性淋巴细胞白血病（CLL）细胞暴露于PMA后，CD21的表达降低，但CD23的表达增加。IL4对CLL细胞中CD21的表达没有影响，但强烈增强了CD23的水平。H7、H8和染料木黄酮各自不同程度地消除了IL4对CLL细胞中CD23表达的影响。这些数据表明，恶性B细胞中丝氨酸/苏氨酸激酶的激活抑制了CD21蛋白的产生，而不同的蛋白激酶似乎参与了不同B淋巴细胞中CD23的上调和下调。
