Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
NATURAL HYBRIDOMAS (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. October 6-11, 1991, Padova/Venice, Italy, p. 88, 1991.. Unique Identifier : AIDSLINE ICDB/92682428 Sinkovics JG; Cancer Inst., St. Joseph's Hosp., Tampa, FL
Abstract:
Knowledge and expertise concerning artificially constructed hybridomas (the Kohler-Milstein technology and its modifications) rapidly increase. Information on naturally occurring hybridomas and on the role of these formations in the course and outcome of malignant disease remains in a most retarded state. The purpose of this presentation is to review examples of natural hybridomas in mice and man. First recognized in 1968-9, the 620 to 818 murine natural hybridomas were reported as 'tetraploid immunoresistant lymphoma.' In this system a murine leukemia virus-producer diploid lymphoma cell fused with an immune plasma cell, producing leukemia virus-neutralizing antibodies. The fusion product cells were tetraploid, synthesized deformed leukemia virus particles and produced specific virus-neutralizing antibodies against the leukemia virus. The fused cells grew in long-term suspension cultures and as ascites tumors in mice. Another murine natural hybridoma is the fusion product of a T-lymphoma cell and a macrophage: the Esb line. In Burkitt's lymphoma, Epstein-Barr virus (EBV)-carrier immortalized B cells and reactive antibody-producer B cells may fuse to form immunoresistant polyploid hybridomas in relapsing patients. Indirect evidence exists for retroviral expression in Hodgkin's disease (HD) based on viral recombination studies. It appears as if a putative human retrovirus acted as an envelope-donor to env gene-defective spleen focus-forming mouse leukemia viruses. The extraordinary diversity of marker expression by Reed-Sternberg (RS) cells can be best explained if the mononuclear HD cell is considered to be a retrovirus-infected interdigitating dendritic cell of lymph nodes that forms hybridomas naturally with Bl and/or Bk cells, or T cells immunologically reactive to retroviral antigens and analogous to the murine 620-to-818 system. RS fusing with each other may form 'quadromas' gaining amplified genes and losing other genes. EBV probably enters HD cells when they fuse with retrovirus-reactive B cells. EBV adds to the immortality and malignancy of RS cells through new surface markers, such as latent membrane protein expression, inducing bcl-2 and thus possibly protecting RS cells against apoptosis. Release of growth factors, cytokines and antibodies from RS cells induces the cellular responses that constitute the histological picture of HD.
Keywords: Antibodies, Monoclonal/*IMMUNOLOGY Antigens, Viral B-Lymphocytes/IMMUNOLOGY Burkitt's Lymphoma/GENETICS/IMMUNOLOGY/MICROBIOLOGY Cell Fusion Gene Amplification Gene Products, env/GENETICS Genes, Viral Herpesvirus 4, Human/*IMMUNOLOGY *Hodgkin's Disease/GENETICS/IMMUNOLOGY/MICROBIOLOGY Leukemia Viruses, Murine/IMMUNOLOGY Ploidies Reed-Sternberg Cells/*IMMUNOLOGY Retroviridae/GENETICS T-Lymphocytes/IMMUNOLOGY ABSTRACT 920830
M9281099
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
