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Characteristics of Potential Lymphoma-inducing Cells in Mice Sensitive or Resistant to Lymphomagenesis by Radiation Leukemia Virus Variants

Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel

The relationship between the H-2-associated responsiveness of mice to radiation leukemia virus variants (A-RadLV and D-RadLV) lymphomagenesis and the characteristics of early occurring potential lymphoma-inducing cells (PLC) among thymus and bone marrow cells of these virus-infected mice was investigated. Sensitivity to virus-induced T-cell lymphomagenesis was shown to involve early occurrence of Thy-positive PLC, found predominantly among thymocytes, whereas resistance was rather related with early identification of PLC-Thy-negative cells mostly among bone marrow cells. PLC were further characterized in the sensitive (BL/6 + A-RadLV) and resistant (BL/6 + D-RadLV) situations by testing in parallel the tumorigenic potential (using the transplantation bioassay method) and type of thymus and bone marrow cell populations separated by different methods such as size fractionation by centrifugal elutriation, cytotoxic elimination of lymphocytes, or panning. The early occurring PLC among thymocytes of BL/6 mice 10–20 days following infection with A-RadLV were shown to be cortisone-resistant, Thy⁺, CD4⁺, and/or CD8⁺ medium size dividing thymocytes. PLC among thymocytes of BL/6 mice + D-RadLV, identified among the medium and large cell fractions, were shown to be cortisone-resistant Thy^-, CD4^-CD8^- lymphocytes. High tumorigenic potential of PLC was demonstrated only among unseparated or separated (on size basis) bone marrow cells of BL/6 + D-RadLV (72–84%), whereas unseparated or separated fractions of bone marrow from BL/6 + A-RadLV had a low lymphomagenic potential (15–20%). The parallelism between the bone marrow fractions that induced optimal thymus cellularity following reconstitution of lethally irradiated mice and optimal lymphomagenicity stress the prothymocyte characteristics of PLC among bone marrow cells of BL/6 mice infected with D-RadLV. It is suggested that in resistant and sensitive haplotypes RadLV variants infect different cell populations and thereby induce PLC which differ in their capacity to present associative MuLV antigens with self H-2.

Received 3/21/89. Revised 11/21/89.