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Clonal Analysis of Radiation Leukemia Virus-induced Leukemic and Preleukemic Murine Cells¹

The Lautenberg Center for General and Tumor Immunology and Department of Molecular Genetics, The Hebrew University, Hadassah Medical School, Jerusalem 91010, Israel

Clonality of radiation leukemia virus (RadLV)-induced thymic lymphomas was determined by detection of rearrangements in the genetic locus coding for the ß chain of the T-cell receptor (Tß). Unique Tß rearrangements were detected in four of six lymphomas. Two of the Tß-rearranged thymic lymphomas and two in which such a rearrangement was not detected had a biallelic deletion of Cß1. With an anti-RadLV monoclonal antibody it was found that 1–2 days after virus inoculation more than one-third of the cells in the thymus were infected by the virus. The frequency of virus-positive cells gradually declined and persisted at 1–2% until the appearance of a clonal lymphoma at which time virtually all the cells in the thymus were virus positive. Transfer of thymocytes from a single, preleukemic mouse 21 days post-virus inoculation into several adoptive recipients resulted in donor-type thymic lymphomas in the majority of the mice. Tß rearrangement analysis revealed that these lymphomas were clonal and derived from different potentially leukemic (preleukemic) cells in the thymus of the donor mouse. Eleven of 15 lymphomas had a biallelic deletion of Cß1. These results suggest that clonal, RadLV-induced thymomas are selected from an oligoclonal, RadLV-infected preleukemic T-cell population.

¹ This work was supported by Concern Foundation, Los Angeles, CA, and the Israel Cancer Research Fund.

² To whom requests for reprints should be addressed, at The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel 91010.

Received 5/21/87. Revised 9/22/87. Accepted 9/23/87.