CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system
CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system
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DOI：
10.4049/jimmunol.166.9.5567
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发表时间：
2001-05-01
影响因子：
4.4
通讯作者：
Fujimoto, J
中科院分区：
文献类型：
--
作者：
Suzuki, T;Kiyokawa, N;Fujimoto, J
糖基磷脂酰肌醇锚定的CD24蛋白是一种B细胞分化抗原，在成熟的静息B细胞上表达，但在Ag刺激后消失。我们用Burkitt淋巴瘤细胞(被认为与生发中心B细胞相关)检测了抗体介导的CD24交联物对人B细胞的生物学效应，观察到1)CD24交联物介导的BL细胞的凋亡；2)CD24交联物与B细胞抗原受体在诱导凋亡中的协同作用。我们还观察到CD24交联后丝裂原活化蛋白激酶的激活，表明CD24介导了导致BL细胞凋亡的细胞内信号转导。虽然CD24没有胞浆部分来传递细胞内的信号，但对糖脂富集膜(GEM)部分的生化分离分析表明，GEM中CD24和Lyn蛋白酪氨酸激酶的结合增强，CD24交联后Lyn激酶活性增加，表明CD24通过GEM依赖的机制介导细胞内信号传递。CD24交联后，CD24和LYN的特定显微辅盖作用支持这一观点，而其他激酶则不是。我们进一步观察到，通过交联诱导细胞凋亡是表达在BL细胞上的GEM相关分子的共同特征，包括GPI锚定蛋白和糖鞘糖脂。CD24介导的细胞凋亡可能为GEM相关分子启动的细胞死亡机制提供了一种模型，GEM相关分子与抗原介导的细胞凋亡的B细胞受体密切相关。
The glycosylphosphatidylinositol-anchored CD24 protein is a B cell differentiation Ag that is expressed on mature resting B cells but disappears upon Ag stimulation. We used Burkitt's lymphoma (BL) cells, which are thought to be related to germinal center B cells, to examine the biological effect of Ab-mediated CD24 cross-linking on human B cells and observed 1) induction of apoptosis in BL cells mediated by cross-linking of CD24; and 2) synergism between the cross-linking of CD24 and that of the B cell receptor for Ag in the effect on apoptosis induction. We also observed activation of mitogen-activated protein kinases following CD24 cross-linking, suggesting that CD24 mediates the intracellular signaling that leads to apoptosis in BL cells. Although CD24 has no cytoplasmic portion to transduce signals intracellularly, analysis of biochemically separated glycolipid-enriched membrane (GEM) fractions indicated enhanced association of CD24 and Lyn protein tyrosine kinase in GEM as well as increased Lyn kinase activity after CD24 cross-linking, suggesting that CD24 mediates intracellular signaling via a GEM-dependent mechanism. Specific microscopic cocapping of CD24 and Lyn, but not of other kinases, following CD24 cross-linking supported this idea. We further observed that apoptosis induction by cross-linking is a common feature shared by GEM-associated molecules expressed on BL cells, including GPI-anchored proteins and glycosphingolipids. CD24-mediated apoptosis in BL cells may provide a model for the cell death mechanism initiated by GEM-associated molecules, which is closely related to B cell receptor for Ag-mediated apoptosis.