DIFFERENTIAL EPSTEIN-BARR-VIRUS GENE-EXPRESSION IN B-CELL SUBSETS RECOVERED FROM LYMPHOMAS IN SCID MICE AFTER TRANSPLANTATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES
DIFFERENTIAL EPSTEIN-BARR-VIRUS GENE-EXPRESSION IN B-CELL SUBSETS RECOVERED FROM LYMPHOMAS IN SCID MICE AFTER TRANSPLANTATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES
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DOI：
10.1128/jvi.69.1.150-155.1995
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发表时间：
1995-01-01
影响因子：
5.4
通讯作者：
MOSIER, DE
中科院分区：
文献类型：
--
作者：
ROCHFORD, R;MOSIER, DE
我们分析了在接受了来自EB病毒（EBV）血清阳性供体的外周血淋巴细胞移植的SCID小鼠中自发产生的人类B细胞肿瘤，以确定EBV基因表达模式是否与肿瘤B细胞的表型变化相关。基于膜CD 23和CD 38的差异共表达，通过细胞分选将肿瘤细胞仅仅分离成两个B细胞亚群。一个亚组显示中等水平的CD 23和CD 38表达（CD 23（int）tCD 38（int）），而第二个亚组具有低水平的CD 23但高水平的CD 38表达（CD 23（lo）CD 38（hi））。CD 23（int）tCD 38（int）细胞增殖指数高，分泌免疫球蛋白少; CD 23（lo）CD 38（hi）细胞增殖指数低，分泌免疫球蛋白多。我们接下来分析了分选的细胞中与潜伏期（EBNA-1、EBNA-2和LMP-1）或裂解周期复制（ZEBRA和gp 350包膜蛋白）相关的病毒转录物。在CD 23（int）CD 38（int）细胞中仅发现潜伏周期转录物，而在CD 23（lo）CD 38（h1）细胞中存在裂解周期转录物和转化病毒。最后，我们从分选的CD 23（int）CD 38（int）细胞中产生了短期分辨细胞系，并将这些细胞转移到SCID受体中。由此产生的继发性肿瘤主要是CD 23（lo）CD 38（hi），表明CD 23（int）CD 38（int）淋巴母细胞样细胞是分化良好的浆细胞样CD 23（lo）CD 38（hi）细胞的前体。这些观察结果进行了讨论的背景下，三步模型EBV相关的淋巴瘤在人类。
We have analyzed the human B-cell tumors that arise spontaneously in SCID mice who have been given transplants of peripheral blood lymphocytes from EpStein-Barr virus (EBV)-seropositive donors to determine if patterns of EBV gene expression are correlated with phenotypic changes in the tumor B cells. Tumor cells mere separated into two B-cell subsets by cell sorting on the basis of differential coexpression of membrane CD23 and CD38. One subset showed intermediate levels of CD23 and CD38 expression (CD23(int)tCD38(int)), while a second subset had low-level CD23 but high-level CD38 expression (CD23(lo)CD38(hi)). The CD23(int)tCD38(int) cells had a high proliferative index and secreted little immunoglobulin in vitro; the CD23(lo)CD38(hi) cells had a low proliferative index and high-level immunoglobulin secretion. We next analyzed the sorted cells for viral transcripts associated with latency (EBNA-1, EBNA-2, and LMP-1) or lytic cycle replication (ZEBRA and gp350 envelope protein). Only latent cycle transcripts were found in CD23(int)CD38(int) cells, whereas lytic cycle transcripts and transforming virus were present in the CD23(lo)CD38(h1) cells. Finally, we generated short-term tell lines from the sorted CD23(int)CD38(int) cells and transferred these cells to SCID recipients. The resulting secondary tumors were predominantly CD23(lo)CD38(hi), suggesting that the CD23(int)CD38(int) lymphoblastoid cells are precursors to the well-differentiated, plasmacytoid CD23(lo)CD38(hi) cells. These observations are discussed in the context of a three-step model for EBV-associated lymphomagenesis in humans.