D'Urso C M, Wang Z G, Cao Y, Tatake R, Zeff R A, Ferrone S
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
J Clin Invest. 1991 Jan;87(1):284-92. doi: 10.1172/JCI114984.
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 that 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.
黑色素瘤细胞系FO-1不表达HLA I类抗原，在与γ干扰素孵育后也不会在细胞表面获得此类抗原。免疫化学研究表明，FO-1细胞能合成HLA I类重链，但不能合成β2-微球蛋白（β2-μ）。后一种异常与缺乏β2-μ mRNA有关，在用γ干扰素孵育的FO-1细胞中仍检测不到该mRNA。该缺陷被确定为B2m基因中的遗传损伤，因为DNA杂交分析检测到B2m基因5'-侧翼区域的第一个外显子以及第一个内含子的一段缺失。在用野生型小鼠B2m基因转染后，黑色素瘤细胞FO-1上重新构建了HLA I类抗原表达，从而证实了内源性B2m基因的异常。在FO-1细胞中发现的缺陷不同于淋巴母细胞系Daudi缺乏HLA I类抗原表达的潜在缺陷，但与导致小鼠淋巴母细胞系R1（TL-）缺乏H-2 I类抗原表达的缺陷非常相似。这些结果表明，B2m基因5'区域的基因重组是B2m基因缺陷中的一种常见机制。除了有助于我们理解黑色素瘤细胞HLA I类抗原表达的分子异常外，FO-1细胞还是分析HLA I类抗原在黑色素瘤细胞生物学及其与免疫系统细胞相互作用中的作用的有用模型。
