CD23 ANTIGEN REGULATION AND SIGNALING IN CHRONIC LYMPHOCYTIC-LEUKEMIA
CD23 ANTIGEN REGULATION AND SIGNALING IN CHRONIC LYMPHOCYTIC-LEUKEMIA
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DOI：
10.1172/jci115717
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发表时间：
1992-04-01
影响因子：
15.9
通讯作者：
SARFATI, M
中科院分区：
文献类型：
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作者：
FOURNIER, S;DELESPESSE, G;SARFATI, M
慢性淋巴细胞性白血病（B-CLL）患者的B淋巴细胞强烈表达CD 23抗原，这是一种在该疾病中具有重要预后意义的表面标志物。因为我们先前报道IL-4在B-CLL上显示出较差的CD 23表达能力，所以我们首先检查了B-CLL上CD 23过表达的潜在可能机制，并发现促分裂原活化的CLL T细胞释放能够与IL-4协同强烈诱导CD 23的可溶性因子。使用中和Ab，我们注意到T细胞衍生的增强活性完全归因于IFN-γ（CD 23对正常B细胞的有效抑制剂）、TNF-α（其对正常B细胞没有作用）和IL-2（其对CLL和正常B细胞都具有轻微的增强作用）的组合作用。此外，在存在或不存在IL-4的情况下，重组IFN-γ以及IFN-α、TNF-α和IL-2（但不包括IL-3、IL-5、IL-6、IL-7和α-光毒素）显著增强B-CLL上的CD 23蛋白和mRNA表达。由于最佳的CD 23表达绝对需要IFN-γ、IL-2、TNF-α（其产生在CLL疾病中增加）和IL-4的组合，因此显示IL-4 mRNA确实在新鲜的T-CLL细胞中表达是相关的。我们接下来检查了CD 23在B-CLL增殖调节中的可能作用。通过F（ab '）2抗-CD 23 MAb而不是Fab片段连接抗原通过CD 23的信号传导抑制了马槟榔诱导的B-CLL DNA合成。结论：CD 23基因在B-CLL疾病中异常调节，CD 23分子的交联向白血病B细胞传递负性生长信号。
B lymphocytes from patients with chronic lymphocytic leukemia (B-CLLs), strongly express the CD23 antigen, a surface marker with significant prognostic importance in this disease. Because we previously reported that IL-4 shows a poor capacity for CD23 expression on B-CLLs, we first examined the possible mechanisms underlying CD23 overexpression on B-CLLs and found that mitogen-activated CLL T cells release soluble factors that are capable, in synergy with IL-4, of strongly inducing CD23. Using neutralizing Abs, we noticed that the T-cell-derived enhancing activity is entirely ascribed to the combined effects of IFN-gamma (potent inhibitor of CD23 on normal B cells), TNF-alpha (which has no effect on normal B cells), and IL-2 (which has a slight enhancing effect on both CLL and normal B cells). Furthermore, recombinant IFN-gamma as well as IFN-alpha, TNF-alpha, and IL-2 (but not IL-3, IL-5, IL-6, IL-7, and lymphotoxin) significantly enhance CD23 protein and mRNA expression on B-CLLs, in the presence or absence of IL-4. Inasmuch as optimal CD23 expression absolutely requires the combination of IFN-gamma, IL-2, TNF-alpha (the production of which is increased in CLL disease), and IL-4, it was relevant to show that IL-4 mRNA is indeed expressed in fresh T-CLL cells. We next examined the possible role of CD23 in the regulation of B-CLL proliferation. Signaling through CD23 via ligation of the antigen by F(ab')2 anti-CD23 MAb but not Fab fragments inhibits the cytokine-induced B-CLL DNA synthesis. It is concluded that the CD23 gene is abnormally regulated in B-CLL disease and that cross-linking of CD23 molecule delivers a negative growth signal to the leukemic B cells.