Masucci M G, Klein E
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
Semin Cancer Biol. 1991 Feb;2(1):63-71.
Burkitt's lymphoma (BL) is a highly malignant B cell tumor characterized by three types of chromosomal translocation which constitutively activate the c-myc oncogene by juxtaposing it to Ig coding sequences. Epstein-Barr virus (EBV) infection, hyperendemic malaria and HIV-caused immunosuppression are thought to contribute to the pathogenesis of the tumor. Cell lines derived from EBV carrying and EBV negative BLs often show altered MHC class I antigen expression. The defects include a lower expression of all HLA class I antigens compared to EBV transformed normal B-blasts, and selective down-regulation of certain HLA-A and HLA-C alleles. As a consequence BL cells are often resistant to cytotoxic T lymphocyte (CTL) mediated destruction. Alleles selective down-regulations are found only in cell lines that maintain the tumor cell phenotype while shift towards a more activated 'B-blast like' phenotype is accompanied by HLA class I up-regulation. A similar pattern of HLA class I expression can be found in a subpopulation of germinal center B cells which express a 'BL like' phenotype. Our findings suggest that the HLA class I expression of BL cells reflects the characteristics of the normal B cell precursor and is probably not the result of immune selection.
伯基特淋巴瘤(BL)是一种高度恶性的B细胞肿瘤,其特征在于三种类型的染色体易位,通过将c-myc癌基因与Ig编码序列并列,从而持续激活该基因。爱泼斯坦-巴尔病毒(EBV)感染、高度地方性疟疾和HIV导致的免疫抑制被认为与该肿瘤的发病机制有关。源自携带EBV和EBV阴性BL的细胞系通常显示出MHC I类抗原表达改变。这些缺陷包括与EBV转化的正常B母细胞相比,所有HLA I类抗原的表达较低,以及某些HLA-A和HLA-C等位基因的选择性下调。因此,BL细胞通常对细胞毒性T淋巴细胞(CTL)介导的破坏具有抗性。等位基因选择性下调仅在维持肿瘤细胞表型的细胞系中发现,而向更活化的“B母细胞样”表型转变则伴随着HLA I类上调。在表达“BL样”表型的生发中心B细胞亚群中可以发现类似的HLA I类表达模式。我们的研究结果表明,BL细胞的HLA I类表达反映了正常B细胞前体的特征,可能不是免疫选择的结果。