EVIDENCE FOR SOMATIC REARRANGEMENT OF IMMUNOGLOBULIN GENES CODING FOR VARIABLE AND CONSTANT REGIONS
EVIDENCE FOR SOMATIC REARRANGEMENT OF IMMUNOGLOBULIN GENES CODING FOR VARIABLE AND CONSTANT REGIONS
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DOI：
10.1073/pnas.73.10.3628
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发表时间：
1976-01-01
影响因子：
11.1
通讯作者：
TONEGAWA, S
中科院分区：
文献类型：
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作者：
HOZUMI, N;TONEGAWA, S
从Balb/c小鼠早期胚胎或MOPC 321浆细胞瘤(又名kappa.链产生菌)，用淀粉液化芽孢杆菌H菌株BamHI限制性内切酶消化至完全。所得DNA片段在制备性琼脂糖凝胶电泳法中按大小分级。携带编码kappa可变区或恒定区的基因序列的DNA片段。与纯化的、125I标记的完整MOPC 321.kappa杂交检测链。M RNA及其3‘-’端的半边。胚胎细胞和浆细胞瘤的基因组杂交模式完全不同。胚胎DNA图谱显示两个组分，其中一个与C基因序列杂交，另一个与V基因序列杂交。肿瘤DNA的图谱显示，与V基因和C基因序列杂交的单一成分比胚胎DNA中的任何一种成分都小(MW=240万)。V.kappa。和C.kappa。在胚胎细胞中，彼此相距一定距离的基因在淋巴细胞分化过程中被连接起来，形成一个连续的多核苷酸延伸。这种连接发生在两条同源染色体上。这些发现与V-C基因连接的模型、特定V.kappa的激活有关。并对免疫球蛋白基因座的等位基因排除进行了讨论。
A high-molecular-weight DNA from Balb/c mouse early embryo or from MOPC 321 plasmacytoma (a .kappa. chain producer) was digested to completion with Bacillus amyloliquefaciens strain H restriction enzyme (BamH I). The resulting DNA fragments were fractionated according to size in preparative agarose gel electrophoresis. DNA fragments carrying gene sequences coding for the variable or constant region of .kappa. chains were detected by hybridization with purified, 125I-labeled, whole MOPC 321 .kappa. mRNA and with its 3''-end half. The pattern of hybridization was completely different in the genomes of embryo cells and of the plasmacytoma. The pattern of embryo DNA showed 2 components, one of which (MW = 6.0 million) hybridized with C-gene sequences and the other (MW = 3.9 million) with V-gene sequences. The pattern of the tumor DNA showed a single component that hybridized with both V-gene and C-gene sequences and that is smaller (MW = 2.4 million) than either of the components in embryo DNA. V.kappa. and C.kappa. genes, which are some distance away from each other in the embryo cells, are joined to form a contiguous polynucleotide stretch during differentiation of lymphocytes. Such joining occurs in both of the homologous chromosomes. Relevance of these findings with respect to models for V-C gene joining, activation of a specific V.kappa. gene, and allelic exclusion in immunoglobulin gene loci is discussed.