ISOTYPE SWITCHING IN A NEOPLASTIC B CELL MODEL BCL 1

这笔赠款支持了对班级转换的各个方面的研究和 淋巴因子在自发性小鼠B白血病BCL1中的诱导。我们的 上一阶段的调查结果促使对 用该模型系统诱导B细胞分化，并与正常B细胞进行比较。基座 在重要的支持数据上，我们已经浓缩了我们持续的努力 分成三个项目。首先，我们想要确定精确的机制和 其对Mu和Gamma1等位基因排除、双重合成的控制 BCL1亚克隆中的链。我们知道这是通过某种形式的 不连续的转录，而不是通过产生一份长的成绩单 覆盖整个VDJ到C-Gamma1区域。第二，我们想要确定 IL-5和IL-6如何与抗原联合诱导增加 BCL1细胞中u转录和DNA复制的速率 通过转染法获得抗原特异性。我们已经鉴定了目标序列 IL-5+Ag的蛋白质-DNA相互作用。我们想要做同样的事情 IL-6加Go追逐两种淋巴因子诱导的因子。第三，我们希望 研究仅在未成熟/成熟B细胞中表达的蛋白质 以免疫球蛋白相关功能为前提的分化阶段 基因表达将会被发现。我们已经从BCL1克隆了两个mRNAs 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.