Apoptosis in splenic B lymphocytes. Regulation by protein kinase C and IL-4.
Apoptosis in splenic B lymphocytes. Regulation by protein kinase C and IL-4.
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DOI：
10.4049/jimmunol.151.6.2965
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发表时间：
1993-09
影响因子：
4.4
通讯作者：
V. Illera;C. Perandones;L. Stunz;D. Mower;R. Ashman
中科院分区：
文献类型：
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作者：
V. Illera;C. Perandones;L. Stunz;D. Mower;R. Ashman
从核体间DNA片段、离体核的次二倍体DNA含量和电镜形态学特征可以看出，来自成年特异性无病原体小鼠的小而致密的脾B淋巴细胞在体外经历了凋亡。无刺激培养12 h后，细胞自发凋亡从70%逐渐单调增加；HA 1004、染料木素和herbimycin A均对细胞凋亡无影响。因此，蛋白激酶C的活性调节细胞凋亡，但没有证据表明蛋白激酶A、G和酪氨酸激酶参与其中。环己亚胺增加细胞凋亡，表明B细胞凋亡可能受到一种或多种不稳定保护蛋白的抑制。无论采用何种凋亡调节方法，流式细胞术测量的凋亡细胞百分比与二苯胺法测量的DNA片段百分比几乎相等。再加上缺乏具有流式细胞术性质的介于正常和凋亡之间的细胞核，这些结果表明，在单个B细胞中，凋亡过程迅速完成。这些数据表明，我们对“休眠”B细胞的生活方式的概念发生了根本性的变化：成熟的脾脏B细胞似乎会因凋亡而死亡，除非被特定的药物（如蛋白激酶C激活剂或IL-4）拯救。而不是一个休眠细胞保持不变，直到它接收到激活信号。
Small dense splenic B lymphocytes from adult specific pathogen-free mice were shown to undergo apoptosis in vitro as indicated by internucleosomal DNA fragmentation, hypodiploid DNA content of isolated nuclei, and morphologic features by electron microscopy. Unstimulated cultures showed spontaneous apoptosis increasing gradually and monotonically from 70% by 12 h; HA 1004, genistein, and herbimycin A all had no effect on apoptosis. Thus, protein kinase C activity regulates apoptosis, but there is no evidence that protein kinases A and G and tyrosine kinases are involved. Cycloheximide increased apoptosis, indicating that apoptosis may be restrained in B cells by the presence of one or more labile protective proteins. The percentage of apoptotic cells measured by flow cytometry and the percentage of fragmented DNA measured by the diphenylamine method were nearly equal, regardless of the method of apoptotic regulation. Together with the absence of nuclei with flow cytometric properties intermediate between normal and apoptotic, these results suggest that in individual B cells apoptosis progresses rapidly to completion. These data suggest a fundamental change in our concept of the life-style of the "resting" B cell: instead of a dormant cell remaining unchanged until it receives activation signals, the mature spleen B cell appears programmed to die by apoptosis unless rescued by specific agents, such protein kinase C activators or IL-4.