Interspecies somatic cell hybrids were generated by fusing the mouse thymic lymphoma cell line, BW5147, with normal human T lymphocytes at different stages of differentiation. Thymocytes, activated peripheral T lymphocytes, or an activated T cell clone were used as human partners, respectively, in three independent fusions. Phenotype and genetic analysis demonstrated that these hybrids preferentially segregated human chromosomes while retaining a complete mouse genetic complement, irrespective of the human partner used for fusion. A large number of T cell differentiation antigens constitutively expressed throughout the T lymphocyte development remained consitutively expressed in the hybrids, irrespective of the maturation stage of human partner used for fusion. In contrast, the expression of other antigens related to a specific stage of T cell development (CD2, CD8), or to an activated state of T lymphocytes (HLA-DR, CD25), was to observed in the hybrids, with no apparent correlation with the segregation of human chromosomes other than, of course, the encoding chromosome. From these results we suggest that the developmental stage of the fusion partners strongly influences the pattern of expression by activating or silencing genes programmed to be expressed in distinct phases of T cell ontogeny.
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机译:通过将小鼠胸腺淋巴瘤细胞系 BW5147 与处于不同分化阶段的正常人 T 淋巴细胞融合,产生种间体细胞杂交种。胸腺细胞、活化的外周 T 淋巴细胞或活化的 T 细胞克隆分别用作人类伴侣,用于三个独立的融合。表型和遗传分析表明,这些杂交种优先分离人类染色体,同时保留完整的小鼠遗传补体,而与用于融合的人类伴侣无关。在整个 T 淋巴细胞发育过程中组成型表达的大量 T 细胞分化抗原在杂交种中保持一致表达,无论用于融合的人类伴侣的成熟阶段如何。相比之下,与T细胞发育的特定阶段(CD2,CD8)或T淋巴细胞的活化状态(HLA-DR,CD25)相关的其他抗原的表达是在杂交种中观察到的,除了编码染色体之外,与人类染色体的分离没有明显的相关性。从这些结果中,我们认为融合伴侣的发育阶段通过激活或沉默编程为在T细胞个体发育的不同阶段表达的基因来强烈影响表达模式。
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