Analysis of the genes in lymphocyte differentiation.

我们正在分析人免疫球蛋白重链基因座中sigma结构的功能：_位于增强子下游，_和_位于和基因之间，_位于s_上游。本研究主要完成了以下几个方面的工作：1）从食虫动物臭鼩（Suncus murinus）的DNA中分离免疫球蛋白基因，并测定其核苷酸序列。比较人、鼠和梭子鱼的核苷酸序列，为我们寻找有生物学意义的区域提供信息.我们建立了一个B细胞系表达IgM和IgG的细胞表面上的转化与高IgM免疫缺陷患者的外周血plood细胞使用EB病毒。结果表明，在双同型细胞中，该转录本中的一个VHDHJH外显子选择性地剪接到C_或C_上，而不发生DNA重排。3）虽然小鼠体内分泌IgD的细胞很少，但在人骨髓瘤中约有1%的患者产生IgD。我们分析了人类IgD骨髓瘤的DNA。数据表明，在人类中，_和_序列之间的同源重组介导了从到的类别转换，并且它是通过姐妹染色单体或子染色体之间的不平等交换发生的。4）我们正在分析^-和^-双生产者中的选择性RNA剪接机制。5）我们正在分析不连续转录之后的反式RNA剪接的发生。

We are analyzing functions of sigma structure in human immunoglobulin heavy chain gene loci: _ located downstream of enhancer, _ and _ located between and genes, _ located upstream of s_ . In this year, we carried out the following experiments.1)We isolated immunoglobulin gene from DNA of the insectivors suncus murinus, and determined its nucleotide sequence. Comparison of nucleotide sequences between man mouse and suncus will give us information for biologically meaningful regions.2. We established a B cell line expressing both IgM and IgG on the cell surface by transformation of peripheral plood cells of a patient with hyper IgM immunodeficiency using epstein-barr viruses. The data showed that in double isotype-bearing cells, one VHDHJH exon in this transript is alternatively spliced to C_ or C_ without DNA rearrangement. The defect in this disease could be at the S-S recombination stage.3) Although the frequency of IgD-secreting cells is extremely low in mouse, about 1% of the patients with myeloma produce IgD in humam. We analyzed dna from human IgD myelomas. The data indicated that homologous recombination between _ and _ sequences mediates class switch from to in human, and that it occurs via unequal crossing over between sister chromatids or daughter chromosomes.4)We are analyzing mechanism alternative rna splicing in ^- and ^- double producers.5)We are analyzing precence of discontinuous transcription followed by trans RNA splicing.