STUDY OF B CELL GROWTH BY EPSTEIN BARR VIRUS

EB病毒（EBV）感染人B细胞并诱导其凋亡。 永生 EBV永生化的分子基础主要是 未知 最近，观察到当EBV永生化细胞被激活时， 在无血清条件下以极低密度培养，增殖停止 细胞就会死亡 然而，添加来自 指数生长的EBV永生化细胞系可以拯救这些细胞， 并促进其扩散。 最近，我们发现 IL-6是EB病毒永生化B细胞自分泌生长因子之一 细胞（Tosato，G.等人，J. Virol.，1990年），但只有约25% 的自分泌生长因子活性归因于IL-6， 剩余的自分泌生长因子活性存在于低分子水平， 重量成分 我们试图鉴定这种低分子量活性。 的 通过凝胶过滤依次完成纯化 色谱、交换色谱、吸附和凝胶渗透 色谱法、反相HPLC和手性相互作用HPLC。 的 通过质谱分析以这种方式纯化的材料。 两 主要成分鉴定为乳酸（LA）和草酸。 合成LA在1至10 mM时刺激EBV-永生化B细胞的生长， 培养上清液中达到的LA浓度为 EBV永生化细胞系。 仅这个分子就被发现 对于所有低分子量自分泌生长因子活性， EBV-永生化B细胞的上清液。 因此，LA是一种自分泌 诱导EBV永生化B增殖的刺激分子 细胞

Epstein-Barr virus (EBV) infects human B cells and induces their immortalization. The molecular basis for EBV immortalization is largely unknown. Recently, it was observed that when EBV immortalized cells are cultured without serum at critically low densities, proliferation ceases and the cells die. However, addition of cell-free supernatants from exponentially growing EBVimmortalized cell lines can rescue these cells from death and promote their proliferation. Recently, we have identified IL-6 as being one of the autocrine growth factors for EBV-immortalized B cells (Tosato, G. et al, J. Virol., 1990) However, only approximately 25% of autocrine growth factor activity is attributable to IL-6 while the remaining autocrine growth factor activity resides in a low molecular weight component. We sought to identify this low molecular weight activity. The purification was accomplished, sequentially, by gel filtration chromatography, exchange chromatography, adsorption and gel permeation chromatography, reverse phase HPLC and hydrophilic-interaction HPLC. The material purified in this manner was analyzed by mass spectrometry. Two major components were identified as lactic acid (LA) and oxalic acid. Synthetic LA stimulated growth in EBV-immortalized B cells at 1 to 10 mM, a concentration of LA achieved in the culture supernatant of EBV-immortalized cell lines. This molecule alone was found to account for all the low molecular weight autocrine growth factor activity in supernatants of EBV-immortalized B cells. Thus, LA is an autocrine stimulatory molecule that induces the proliferation of EBV-immortalized B cells.