Analysis of the genes in lymphocyte differentiation.

我们分析了sigma结构在人免疫球蛋白重链基因位点的功能：位于增强子下游的_和位于两个基因之间的_和位于s_上游的_。在这一年中，我们进行了以下实验。1)从食虫鼠尾鼠DNA中分离免疫球蛋白基因，确定其核苷酸序列。比较人类小鼠和猕猴之间的核苷酸序列将为我们提供生物学上有意义的区域信息。我们利用epstein-barr病毒转化高IgM免疫缺陷患者外周血细胞，建立了在细胞表面表达IgM和IgG的B细胞系。数据表明，在双同型细胞中，该转录本中的一个VHDHJH外显子被选择性地剪接到C_或C_上，而没有DNA重排。本病的缺陷可能处于S-S重组阶段。3)虽然小鼠体内分泌IgD的细胞频率极低，但人类骨髓瘤患者体内约有1%的细胞产生IgD。我们分析了来自人类IgD骨髓瘤的dna。结果表明，_和_序列之间的同源重组介导了人类从_到_的类别转换，这种转换是通过姐妹染色单体或子染色体之间的不平等杂交发生的。4)我们正在分析^-和^-双生产者的rna剪接机制。5)我们正在分析反式RNA剪接后的不连续转录的优先性。

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.