Functionally active Epstein-Barr virus-transformed follicular dendritic cell-like cell lines.

Functionally active Epstein-Barr virus-transformed follicular dendritic cell-like cell lines.
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DOI:
10.1084/jem.179.4.1173
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发表时间:
1994-04-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
de Groot C
de Groot C
中科院分区:
其他
文献类型:
--
作者:
Lindhout E;Lakeman A;Mevissen ML;de Groot C

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滤泡树突状细胞(FDC)是唯一的非淋巴样细胞,只在生殖中心发现。FDC可以基于细胞表面标志物的特征集与其他辅助细胞区分开。已知FDC能够拯救生殖中心B细胞免于凋亡。为了探讨FDC在生发中心反应期间B细胞选择和成熟过程中的作用,我们尝试建立因子非依赖性永生化FDC样细胞系。由于新鲜分离的FDC表达EB病毒(EBV)受体CD 21,因此我们尝试对分离的FDC进行EB病毒转化。在将富含FDC的细胞群与EBV孵育后,获得由缓慢复制的非常大的细胞组成的细胞系。这些细胞系具有成纤维细胞样形态,但通过显示不同的表型(包括细胞间粘附分子1、CD 40和CD 75表达),可与几种人成纤维细胞系明确区分开来。检测EB病毒编码的蛋白潜伏膜蛋白1和EB病毒核抗原2在我们的FDC样细胞系暗示成功的EB病毒转化。FDC样细胞能够结合非自体B细胞并保护后者免于凋亡。B细胞与FDC样细胞的结合依赖于通过淋巴细胞功能相关抗原1/细胞间粘附分子1的粘附,并且与其他人所描述的帝国主义模式非常相似。这些数据表明,FDC可以成功地被EBV感染,并且所获得的细胞系与新鲜分离的FDC共享表型和功能特征。
Follicular dendritic cells (FDC) are unique nonlymphoid cells found only in germinal centers. FDC can be distinguished from other accessory cells based on a characteristic set of cell surface markers. It is known that FDC are able to rescue germinal center B cells from apoptosis. To investigate the role of FDC in the process of selection and maturation of B cells during germinal center reactions, we tried to establish factor-independent immortalized FDC-like cell lines. Because freshly isolated FDC express the Epstein-Barr Virus (EBV) receptor CD21, we attempted EBV transformation on isolated FDC. After incubation of FDC-enriched cell populations with EBV, cell lines were obtained consisting of slowly duplicating very large cells. These cell lines have a fibroblast-like morphology but could be clearly distinguished from several human fibroblast cell lines by displaying a different phenotype including intercellular adhesion molecule 1, CD40, and CD75 expression. Detection of the EBV-encoded proteins latent membrane protein 1 and Epstein-Barr virus nuclear antigen 2 in our FDC-like cell lines implicated successful EBV transformation. FDC-like cells are able to bind nonautologous B cells and preserve the latter from apoptosis. The binding of B cells to FDC-like cells is dependent on adhesion via lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and closely resembles the pattern of emperipolesis as described by others. These data demonstrate that FDC can be successfully infected by EBV, and that the cell lines obtained share phenotypic and functional characteristics with freshly isolated FDC.