Lack of HLA Class I Antigen Expression by Cultured Melanoma Cells FO-1 Due to a Defect in B2m Gene Expression

J Clin Invest. 1991 Jan;87(1):284-92. doi: 10.1172/JCI114984.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA / analysis
  • Gene Expression*
  • Histocompatibility Antigens Class I / analysis*
  • Histocompatibility Antigens Class I / biosynthesis
  • Humans
  • Interferon-gamma / pharmacology
  • Killer Cells, Natural / immunology
  • Melanoma / immunology*
  • Mice
  • RNA, Messenger / analysis
  • Transfection
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / genetics*

Substances

  • Histocompatibility Antigens Class I
  • RNA, Messenger
  • beta 2-Microglobulin
  • Interferon-gamma
  • DNA