Plasmacytoid Differentiation of Epstein-Barr Virus-Transformed B Cells in vivo is Associated with Reduced Expression of Viral Latent Genes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-01, Vol.90 (1), p.352-356
• Main Authors: Rochford, Rosemary, Hobbs, Monte V., Garnier, Jeanne-Luce, Cooper, Neil R., Cannon, Martin J.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antibodies, Monoclonal; Antigens, CD - analysis; Antigens, Viral - genetics; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - physiology; Biological and medical sciences; Cell Cycle; Cell Differentiation - physiology; Cell lines; Cells, Cultured; DNA-Binding Proteins - genetics; Epstein Barr virus infections; Epstein-Barr virus; Epstein-Barr Virus Nuclear Antigens; Flow Cytometry; Gene Expression; Genes; Genes, Viral; Genetic Vectors; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Human viral diseases; Humans; Infectious diseases; Medical disorders; Medical research; Medical sciences; Mice; Mice, SCID; Phenotypes; Plasma cells; Plasmacytoma; Polymerase Chain Reaction; Ribosomal Proteins - genetics; RNA; Tumor cell line; Tumor Cells, Cultured; Tumors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.1.352

The Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders that arise in immunosuppressed individuals are considered to resemble EBV-transformed in vitro lymphoblastoid cell lines (LCLs) with a mature activated B-cell phenotype. In this study of human lymphoproliferative disorders in the severe combined immunodeficiency mouse model, however, we demonstrate that EBV-infected tumor cells are not LCL-like but are predominantly plasmacytoid and that this phenotype correlates with reduced expression of EBV latent genes. B-cell tumors developed within 3-6 weeks after injection of LCLs into severe combined immunodeficiency mice. The tumors and the injected LCLs were analyzed by flow cytofluorometry for B-cell differentiation and activation markers and by ribonuclease protection assay for cellular and viral gene expression. No differences in the expression of CD19 and CD21 were observed. However, a decrease in CD23, CD11a (lymphocyte function-associated antigen LFA-1), and CD58 (LFA-3) expression and an increase in CD38 (a plasma-cell-associated antigen), CD54 (intracellular adhesion molecule ICAM-1), and HLA class I in the tumor cells relative to the LCLs was observed. Two-color flow cytofluorometric analysis showed that the predominant population (>80%) in LCLs was CD23hi/CD38loand that the major population in LCL-derived tumors was CD23lo/CD38hi. Cell cycle analysis showed that, in contrast to actively cycling LCLs, the majority of tumor cells had exited the cell cycle and were restricted to G0/G1phase. Finally, and most important, a reduction in mRNA for the EBV latent genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein (LMP1) was observed in the tumors.