PROPERTIES OF LYMPHOID TUMOR CELLS IN VIVO AND IN VITRO

宿主T细胞生殖中心（GC）衍生的B淋巴瘤细胞相互作用 将被审查。 一个需要回答的核心问题是， SJL小鼠淋巴瘤发生的原因是：是什么导致高mtv-29编码 vSAg转录以及它如何与这些基因的GC起源相关 淋巴瘤（RCS）？ 肝脏和RCS DNA中mtv-29的5' LTR将被测定。 测序以确定5 'LTR是在所有细胞中有缺陷还是仅在所有细胞中有缺陷 以解释vSAg起始位点位于末端区域 mtv-29。 该vSAg表达的调节将通过使用 横切报告构建体并寻找特异性结合因子 对于mtv-29中的区域，在RCS和正常GC中表达，但在其他GC中不表达。 B细胞。 将研究体内促生长的机制， 包括c57 L小鼠中v β 16 + T细胞的命运。 的 Vbeta 16 T细胞在发育中的原发性骨髓瘤小鼠PBL中的表达 将跟踪淋巴瘤，并观察抗V β 16对肿瘤生长的影响 体内评价。 将尝试识别继发性致癌 导致持续增殖和缺乏分化的事件， e 淋巴瘤细胞 将确定RCS、正常隔离GC 和NJ 101细胞对自发性和糖皮质激素的抗性不同 诱导凋亡。 在形态学上， 来自bcl-2转基因和正常SJL小鼠的异常和正常GC将 是研究。 评价~反向免疫现象是否 监测~可能适用于人类，CD 4 + T细胞浸润 将检查人GC衍生的淋巴瘤的V β或Va TCR 可能反映对特定Ag或v β的单克隆反应的模式 对SAg的限制性反应。

The host T cell germinal center (GC) derived B lymphoma cell interaction will be examined. A central question to be answered about the lymphomagenesis in SJL mice is: What causes the high mtv-29 encoded vSAg transcription and how does it relate to the GC origin of these lymphomas (RCS)? The 5' LTR of mtv-29 in liver and RCS DNA will be sequenced to determine whether the 5'LTR is defective in all cells or only in RCS cells to explain that the vSAg initiation site is in the end region mtv-29. Regulation of the expression of this vSAg will be studied by using transection of reporter constructs and looking for specific binding factors for regions in mtv-29, expressed in RCS and normal GC but not in other B cells. The mechanism of the growth promotion in vivo will be studies, including the fate of vbeta16+ T cells in c57L mice will be analyzed. The vbeta16 T cell representation in PBL of mice with developing primary lymphomas will be followed and the effect of anti-vbeta16 on tumor growth in vivo evaluated. Attempts will be made to identify secondary oncogenic events that cause continued proliferation and a lack of differentiation in e lymphoma cells. It will be determined whether RCS, normal isolated GC and NJ101 cells differ in resistance to spontaneous and glucocorticosteroid induced apoptosis. The expression of several oncogenes in morphologically abnormal and normal GCs from bcl-2 transgenic and normal SJL mice will be studies. To evaluate whether the phenomenon of ~reverse immune surveillance~ may be applicable to humans, CD4+ T cell infiltrates in human GC-derived lymphomas will be examined for Vbeta or Va TCR patterns that might reflect monoclonal responses to specific Ag or v beta restricted responses to a SAg.