GERMINAL CENTERS, ANTIBODY PRODUCTION, AND LYMPHOMA

生发中心、抗体产生和淋巴瘤

• 批准号: 2442207
• 负责人: G. J THORBECKE
• 金额: $ 31.78万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2442207
• 关键词: B lymphocyte; age difference; aging; antibody formation; apoptosis; gene expression; genetically modified animals; helper T lymphocyte; immune tolerance /unresponsiveness; immunoglobulin D; immunoglobulin genes; in situ hybridization; laboratory mouse; lymphatic tissue; lymphoma; major histocompatibility complex; northern blottings; polymerase chain reaction; superantigens

In this project #2 of an IRPG request, the relationship between germinal center (GC) formation in lymphoid tissues and spontaneous lymphomas (RCS) in aging SJL mice will be explored with the aid of a few transgenic mouse models. Our recent findings show that these lymphomas express an mtv- "RCS"-LTR encoded superantigen (vSAG) and receive growth promoting help through the cytokine formation induced in the Vbeta16 T cells that this vSAG stimulates. The possibility that normal GC cells which are thought to be the precursor cells of RCS, express this same vSAG in SJL mice will be examined, making use of I-E transgenic mice that specifically express I-E in GC and not in other B cells. Three different constructs will be used to prepare mtv-RCS-LTR transgenic SJL mice, in one of these the transgene expression targeted to B cells, to determine the influence of this transgene on Vbeta16 T cell deletion, on GC formation and on paraprotein production. The effect of the bcl-2 transgene in SJL mice on GC formation and on their resistance to glucocorticosteroid-induced apoptosis will be studied in parallel with effects on antibody and paraprotein production, as well as lymphoma development. In addition, mice transgenic for an anti-TNP IgH + L chain combination (Sp6), consisting of mu-kappa, will be studied for their ability to make anti-TNP bearing GC cells. Their sensitivity to tolerance induction at the GC precursor cell level (J11D1o) in the presence and absence of the bcl-2 transgene will be evaluated. The Ig gene V regions of lymphomas arising in Sp6 transgenic mice, will be examined for somatic mutations. In all these experiments, a close collaboration will be maintained with Dr. N.M. Ponzio, who will be examining the effect of some of the transgenes on lymphoma formation and the influence of Vbeta16 T cell modulation on lymphoma growth in project #1 of this IRPG.

在这个IRPG请求的项目#2中， 淋巴组织和自发性淋巴瘤（RCS）中的中心（GC）形成 在一些转基因小鼠的帮助下， 模型 我们最近的发现表明这些淋巴瘤表达一种mtv- “RCS”-LTR编码的超抗原（vSAG）并接受生长促进帮助 通过在V β 16 T细胞中诱导的细胞因子形成， vSAG刺激。 被认为是正常的胃癌细胞 作为RCS的前体细胞，在SJL小鼠中表达相同的vSAG， 使用特异性表达的I-E转基因小鼠进行检查， I-E在GC中，而在其他B细胞中不存在。 三种不同的结构将 用于制备mtv-RCS-LTR转基因SJL小鼠，在这些小鼠之一中， 靶向B细胞的转基因表达，以确定 这种转基因对V β 16 T细胞缺失、GC形成和 副蛋白生产。 bcl-2转基因对SJL小鼠免疫功能的影响 GC的形成及其对糖皮质激素诱导的抗性 细胞凋亡将与对抗体的影响平行研究， 副蛋白的产生以及淋巴瘤的发展。 此外，本发明还提供了一种方法， 抗TNP IgH + L链组合转基因小鼠（Sp 6）， 将研究它们产生抗TNP的能力， 带有GC细胞。 它们对GC耐受诱导的敏感性 前体细胞水平（J11 D1 o）在存在和不存在bcl-2的情况下 将评估转基因。 淋巴瘤发生的IG基因V区 在Sp 6转基因小鼠中，将检查体细胞突变。 在所有 在这些实验中，将与N. M.博士保持密切合作。 他将研究一些转基因对 淋巴瘤的形成和V β 16 T细胞调节对淋巴瘤形成的影响 淋巴瘤生长在这个IRPG的项目#1。