title: Radiation leukemia virus-induced thymic lymphomas express a restricted repertoire of T-cell receptor V beta gene products.
abstract: We have investigated the phenotypic changes that take place during the process of neoplastic transformation in the thymocytes of C57BL/Ka mice infected by the radiation leukemia virus (RadLV). By the combined use of antibodies against the envelope glycoprotein gp70 of RadLV, the transformation-associated cell surface marker 1C11, and the CD3-T-cell receptor (TCR) complex, we found that in the RadLV-infected thymus, the earliest expression of viral gp70 is in 1C11hi cells; a small but significant percentage of these cells also express CD3. A first wave of viral replication, manifested by the expression of high levels of gp70 in thymocytes (over 70% positive), reaches a peak at 2 weeks; during this period, no significant changes are observed in the expression of 1C11 or CD3. The population of gp70+ cells is drastically reduced at 3 to 4 weeks after infection. However, a second cohort of gp70+ cells appears after 4 weeks, and these cells express high levels of 1C11 and TCR determinants as well. RadLV-induced lymphomas differ from normal thymocytes in their CD4 CD8 phenotype, with domination by one or more subsets. Characterization of TCR gene rearrangements in RadLV-induced lymphomas shows that most of these tumors are clonal or oligoclonal with respect to the J beta 2 TCR gene, while the J beta 1 TCR gene is rearranged in a minority (4 of 11) of lymphomas. TCR V beta repertoire analysis of 12 tumors reveals that 6 (50%) express exclusively the V beta 6 gene product, 2 (17%) are V beta 5+, and 1 (8%) each are V beta 8+ and V beta 9+. In normal C57BL/Ka mice, V beta 6 is expressed on 12%, V beta 5 is expressed on 9%, V beta 8 is expressed on 22%, and V beta 9 is expressed on 4% of TCRhi thymocytes. Thus, it appears that RadLV-induced thymic lymphomas are not randomly selected with respect to expressed TCR V beta type.
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5468.
authors.forename: A
authors.initials: A
authors.lastname: Sen-Majumdar
authors.forename: I L
authors.initials: IL
authors.lastname: Weissman
authors.forename: G
authors.initials: G
authors.lastname: Hansteen
authors.forename: J
authors.initials: J
authors.lastname: Marian
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
authors.forename: M
authors.initials: M
authors.lastname: Lieberman
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002471:Cell Transformation, Neoplastic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007942:Leukemia, Experimental / Q000276:immunology / Q000382:microbiology; D008223:Lymphoma / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016721:Radiation Leukemia Virus / Q000254:growth & development*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D012192:Retroviridae Infections / Q000276:immunology*; D015682:Retroviridae Proteins, Oncogenic / Q000032:analysis; D012641:Selection, Genetic; D013950:Thymus Gland / Q000166:cytology; D013953:Thymus Neoplasms / Q000276:immunology* / Q000382:microbiology; D014412:Tumor Virus Infections / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000032:analysis; D014779:Virus Replication
chemical_list: D000943:Antigens, Differentiation; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins