GERMINAL CENTERS, ANTIBODY PRODUCTION, AND LYMPHOMA

在这个IRPG请求的项目#2中，生发之间的关系 淋巴组织和自发性淋巴瘤(RCS)的中心(GC)形成 将在几只转基因小鼠的帮助下探索衰老的SJL小鼠 模特们。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)和接受促生长帮助 通过在Vbeta16T细胞中诱导细胞因子的形成，这 VSAG具有刺激作用。正常的GC细胞被认为是 作为RCS的前体细胞，在SJL小鼠体内表达相同的vSAG将 利用I-E转基因小鼠进行检测，这些转基因小鼠可以特异性地表达 I-E在GC中表达，在其他B细胞中不表达。三种不同的构造将是 用于制备MTV-RCS-LTR转基因SJL小鼠，在其中一种 以B细胞为靶点的转基因表达，以确定对 该转基因对Vbeta16 T细胞缺失、GC形成等的影响 副蛋白生产。转基因bcl2基因对SJL小鼠生长发育的影响 GC的形成及其对糖皮质激素耐药的研究 细胞凋亡的研究将与对抗体和 副蛋白的产生，以及淋巴瘤的发展。此外, 转抗TNP IgH+L链组合(Sp6)的小鼠， 由Mu-kappa组成，将研究它们制造抗TNP的能力 有GC细胞。他们对GC耐受诱导的敏感性 Bcl2存在和不存在时的前体细胞水平(J11D1o) 将对转基因进行评估。淋巴瘤发病的免疫球蛋白基因V区 在Sp6转基因小鼠中，将检测体细胞突变。总而言之， 在这些实验中，将与N.M.博士保持密切合作。 Ponzio，他将研究一些转基因对 淋巴瘤的形成及Vbeta16T细胞调节对其的影响 此IRPG项目1中的淋巴瘤生长。

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.