LACK OF HLA CLASS-I ANTIGEN EXPRESSION BY CULTURED MELANOMA-CELLS FO-1 DUE TO A DEFECT IN B2M GENE-EXPRESSION
LACK OF HLA CLASS-I ANTIGEN EXPRESSION BY CULTURED MELANOMA-CELLS FO-1 DUE TO A DEFECT IN B2M GENE-EXPRESSION
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DOI：
10.1172/jci114984
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发表时间：
1991-01-01
影响因子：
15.9
通讯作者：
FERRONE, S
中科院分区：
文献类型：
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作者：
DURSO, CM;WANG, ZG;FERRONE, S
黑色素瘤细胞株FO-1不表达HLAI类抗原，与干扰素-γ孵育后不能在细胞表面获得这些抗原。免疫化学研究表明，FO-1细胞合成HLAI类重链，但不合成β-2-微球蛋白(β-2-MU)。后一种异常与缺乏β-2-mumRNA有关，在与干扰素-γ孵育的FO-1细胞中仍未检测到该基因。由于DNA杂交分析检测到B2M基因5‘侧翼区的第一个外显子和第一内含子的一段缺失，因此该缺陷被鉴定为B2M基因的遗传损伤。将野生型小鼠B2M基因导入黑色素瘤细胞FO-1后，重组了HLAI类抗原的表达，从而证实了内源性B2M基因的异常。FO-1细胞中发现的缺陷与淋巴母细胞Daudi缺乏HLAI类抗原表达的根本原因不同，但与小鼠淋巴母细胞R1(TL-)缺乏HLAI类抗原表达的原因非常相似。这些结果提示，B2M基因5‘端的基因重组是B2M基因缺陷的一种复发机制。除了有助于我们了解黑色素瘤细胞表达HLAI类抗原的分子异常外，FO-1细胞还为分析HLAI类抗原在黑色素瘤细胞生物学中的作用及其与免疫系统细胞的相互作用提供了一个有用的模型。
The melanoma cell line FO-1 does not express HLA class I antigens and does not acquire them on the cell surface after incubation with IFN-gamma. Immunochemical studies showed that FO-1 cells synthesize HLA class I heavy chain, but do not synthesize beta-2-microglobulin (beta-2-mu). The latter abnormality is associated with lack of beta-2-mu mRNA which remains undetectable in FO-1 cells incubated with IFN-gamma. The defect was identified as a genetic lesion in the B2m gene, since DNA hybridization analysis detected a deletion of the first exon of the 5'-flanking region, and of a segment of the first intron of the B2m gene. HLA class I antigen expression was reconstituted on melanoma cells FO-1 after transfection with the wild-type mouse B2m gene, thereby confirming the abnormality of the endogenous B2m gene.The defect identified in FO-1 cells is distinct from the underlying the lack of HLA class I antigen expression by lymphoblastoid cells Daudi, but is remarkably similar to that causing lack of H-2 class I antigen expression by mouse lymphoblastoid cells R1 (TL-). These results suggest that genetic recombination in the 5' region of the B2m gene is a recurrent mechanism in B2m gene defects. In addition to contributing to our understanding of molecular abnormalities in HLA class I antigen expression by melanoma cells, FO-1 cells represent a useful model for analyzing the role of HLA class I antigens in the biology of melanoma cells and in their interaction with cells of the immune system.