ISOTYPE SWITCHING IN A NEOPLASTIC B-CELL MODEL BCL 1

这项拨款资助了有关转班的各个方面的研究， 自发性小鼠B白血病中的淋巴因子诱导，BCL 1。我们 上一个时期的调查结果促使对 使用该模型系统的B细胞分化和正常B细胞。基于 在重要的支持数据上，我们浓缩了我们持续的努力， 分为三个项目。首先，我们要确定确切的机制， 其对Mu和γ 1等位基因排斥的双重合成的控制 BCL 1亚克隆中的链。我们知道这是通过某种形式的 不连续转录，而不是通过产生“长转录本” 覆盖整个VDJ到C-γ 1区域。第二，我们要确定 IL-5和IL-6如何与抗原联合诱导增加 在BCL 1细胞中的u转录和DNA复制率呈现 抗原特异性转染。我们已经确定了目标序列 IL-5+Ag的蛋白质-DNA相互作用。我们想做同样的事情， IL-6加IL-6后，两种淋巴因子诱导的因子。第三，我们要 研究仅在未成熟/成熟B细胞中表达的蛋白质 分化阶段基于与IG相关的功能 基因表达将被发现。我们从BCL 1中克隆了两种mRNA， 满足细胞类型和阶段特异性的标准。

This grant has supported studies on various aspects of class switching and lymphokine induction in the spontaneous murine B leukemia, BCL1. Our findings during the last period have prompted a broader investigation of B cell differentiation using this model system and normal B cells. Based on significant supporting data, we have condensed our continuing efforts into three projects. First, we want to determine the precise mechanism and its control for allelically excluded, dual synthesis of mu and gamma1 chains in BCL1 subclones. We know that this occurs by some form of discontinuous transcription, and not by production of a 'long transcript' covering the entire VDJ to C-gamma1 region. Second, we want to determine precisely how IL-5 and IL-6 in conjunction with antigen induce increased rates of u transcription and DNA replication in BCL1 cells rendered antigen-specific by transfection. We have identified the target sequences and the protein-DNA interactions for IL-5+Ag. We want to do the same with IL-6 plus go after the factors induced by both lymphokines. Third, we want to study proteins expressed only at the immature/mature B cell differentiation stage based on the premise that functions relevant to Ig gene expression will be discovered. We have cloned from BCL1 two mRNAs that satisfy the criteria of cell type- and stage-specificity.