Defective class II transactivator expression in a B lymphoma cell line

T. Prod'homme, B. Drénou, C. De Ruyffelaere, G. Barbieri, W. Wiszniewski, C. Bastard, D. Charron, Catherine Alcaide-Loridan

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Loss of MHC class II expression in B-cell lymphoma has been associated with a higher tumorigenicity resulting from lower titers of tumor-infiltrating lymphocytes. This report aims towards the identification of the molecular mechanism leading to defective MHC class II expression in a B-cell lymphoma cell line, Rec-1. We evidenced a coordinated alteration of HLA-D gene transcription, reminiscent of B lymphoblastoid cell lines from patients with MHC class II deficiency. Genetic complementation performed between these cell lines and the lymphoma cells indicated that Rec-1 is altered in the MHC2TA gene. MHC2TA encodes the class II transactivator (CIITA), the master regulator of HLA-D gene expression. However, the coding sequence of the Rec-1 CIITA transcript did not reveal any mutation that could hamper the activity of the encoded protein. In agreement with the genetic complementation analysis, we evidenced a highly residual CIITA protein expression in the Rec-1 cell line resulting from a transcriptional defect affecting MHC2TA expression. Anti-HLA-DR monoclonal antibody treatment has proved efficient in the destruction of B lymphoma cells. Our data indicate that the appearance of variants losing CIITA, and thereby HLA-DR, expression will require a thorough monitoring during such immunotherapy protocols.

Original languageEnglish (US)
Pages (from-to)832-840
Number of pages9
JournalLeukemia
Volume18
Issue number4
DOIs
StatePublished - Apr 2004

Keywords

  • Gene regulation
  • MHC
  • Transcription factor
  • Tumor immunity

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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  • Cite this

    Prod'homme, T., Drénou, B., De Ruyffelaere, C., Barbieri, G., Wiszniewski, W., Bastard, C., Charron, D., & Alcaide-Loridan, C. (2004). Defective class II transactivator expression in a B lymphoma cell line. Leukemia, 18(4), 832-840. https://doi.org/10.1038/sj.leu.2403315