Zeff R A, Zhao Y F, Tatake R, Lachman H, Borriello F, Nathenson S G
Department of Pathology, University of Connecticut Health Center, Farmington 06032.
Blood. 1991 Jul 15;78(2):524-32.
Numerous tumor cell lines of leukemic origin are known to modulate cell surface expression of major histocompatibility complex (MHC) class I antigens resulting in alterations in their immune detection and tumorigenicity. We have been studying the mechanisms responsible for attenuation of MHC class I gene expression in an H-2 heterozygous (H-2b x H-2d) Abelson-Murine leukemia virus (A-MuLV)-transformed leukemic cell line (designated R8). Here we report that treatment of the R8 cell line with the protein synthesis inhibitor cycloheximide (CHX) increased H-2Kb steady-state messenger RNA (mRNA) levels several fold. The induced H-2Kb mRNA transcripts were functional, as demonstrated by their ability to be translated into immunoprecipitable H-2Kb alloantigen. H-2Kb null variants derived from the R8 cell line were shown to be the product of both cis- and trans-acting mechanisms, insomuch as the treatment of R8-derived H-2Kb non-expressor lines with CHX re-established expression of H-2Kb mRNA to the same extent as transfection of the variant cell line with the wild-type H-2Kb gene. Such findings indicate that downregulation of MHC class I gene expression is constitutive for the R8 leukemic cell line, a phenomenon that may be related to the immature pre-B-cell phenotype of this A-MuLV transformant.
已知许多源自白血病的肿瘤细胞系可调节主要组织相容性复合体（MHC）I类抗原的细胞表面表达，从而改变其免疫检测和致瘤性。我们一直在研究负责H-2杂合（H-2b×H-2d）阿贝尔森-鼠白血病病毒（A-MuLV）转化的白血病细胞系（命名为R8）中MHC I类基因表达减弱的机制。在此我们报告，用蛋白质合成抑制剂环己酰亚胺（CHX）处理R8细胞系可使H-2Kb稳态信使核糖核酸（mRNA）水平提高数倍。诱导产生的H-2Kb mRNA转录本具有功能，这可通过其被翻译成可免疫沉淀的H-2Kb同种抗原的能力得以证明。源自R8细胞系的H-2Kb无效变体显示是顺式和反式作用机制的产物，因为用CHX处理源自R8的H-2Kb非表达细胞系可使H-2Kb mRNA的表达恢复到与用野生型H-2Kb基因转染变体细胞系相同的程度。这些发现表明，MHC I类基因表达的下调对于R8白血病细胞系是组成性的，这一现象可能与这种A-MuLV转化体的未成熟前B细胞表型有关。
