Mechanisms of allele-selective down-regulation of HLA class I in Burkitt's lymphoma

✍ Scribed by Marta P. Imreh; Qian-Jin Zhang; Pedro O. De Campos-Lima; Stephan Imreh; Peter Krausa; Michael Browning; George Klein; Maria G. Masucci

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: French
• Weight: 852 KB
• Volume: 62
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910620117

✦ Synopsis

Abstract

Burkitt lymphomas (BL) that arise in HLA‐A11‐positive individuals are characterized by selective loss/down‐regulation of the HLA AII polypeptide. We have investigated the molecular basis of such down‐regulation by comparing 5 pairs of BL lines and Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cell lines (LCL) derived from the normal B cells of the same individuals. The presence of apparently intact HLA A11 genes was confirmed in all 5 BL/LCL pairs by polymerase chain reaction (PCR) typing and by Southern‐blot hybridization with HLA A locus‐specific probes. Northern‐blot analysis with locus‐and allele‐specific probes revealed a significantly lower expression or absence of A11‐specific mRNA in all 5 BL lines compared to the corresponding LCLs. Up‐regulation of Al1 ‐specific mRNA was achieved by IFNα treatment of 2 BL lines with low HLA A11 expression (BL‐28 and BL‐72) while the treatment had no effect in 3 BL fines (WWI ‐BL, WW2‐BL and BL41) that did not express the endogenous gene. HLA A11 expression was restored by transfection of the gene in WWI‐BL whereas transfectants of BL‐41 remained Al1‐negative. An HLA‐A11‐promoter‐driven chloramphenicol acetyl transferase reporter gene (pAl1 CAT) was active in WWI‐BL but not in BL‐41. HLA‐A11 was expressed in hybrids of BL‐41 with an A11‐positive LCL, while expression of the endogenous HLA A11 gene could not be restored by fusion of BL‐41 with an A11 ‐negative LCL, although an adequate set of transcription factors was present in the hybrid. Our results suggest that genetic defects and lack of transcription factors may contribute to the selective downregulation of HLA A11 in BL cells. © 1995 Wiley‐Liss Inc.