Appearance and distribution of virally determined antigens in lymphoid organs of mice during leukemogenesis by moloney leukemia virus

Abstract

Newborn mice were inoculated with the Moloney murine leukemia virus (M-MuLV) and changes in antigen expression and virus production in thymus, spleen and lymph nodes were studied during the preleukemic period. Viral p30 and gp70-related antigens were detected in M-MuLV inoculated mice, as well as in controls. The frequency of detection increased with age in both groups and the fraction of p30 + and gp70 + cells was higher at any time in the thymus than in spleen and lymph nodes. The M-MuLV determined cell surface antigen (MCSA) was detected in virus-inoculated mice only and not in controls. Preleukemic thymus cells were MCSA + already at 1 month of age, whereas spleen and lymph nodes of the same animals were MCSA −. In the latter tissues, an increase in the fraction of MCSA + cells was proportional to the fraction of Thy-1.2 + cells. Leukemia cells were positive for both MCSA and Thy-1.2. Thymus cells produced significantly higher amounts of ecotropic virus (NB-tropic, large XC-plaque) than spleen and lymph nodes. Xenotropic virus (focus induction in S +L − mink cells) was only detected in 3 months old or older mice. There was no correlation between MCSA expression and production of either eco- or xenotropic virus in individual mice. However, thymus cells were often MCSA + and produced large amounts of ecotropic and xenotropic virus. One-third of the M-MuLV inoculated mice developed thymomas, consisting of cells with 41 chromosomes, due to a trisomic chromosome 15. Two-thirds of mice developed spleen and lymph node enlargement with normal diploid karyotype. Transfer of trisomic cells to syngeneic irradiated recipients of the opposite sex gave rise to solid tumors of donor type at the site of inoculation. Transfer of spleen cells with normal diploid karyotype gave splenomegaly in the recipient. As judged from the sex marker, the splenomegalies were of two types. Either consisting of host cells (new induction) or donor cells (transplantation). Preleukemic MCSA + thymus cells were similarly transferred and the cells were non-tumorigenic. Instead, virus released from the thymus cells infected the hosts and induced new leukemias. Thus the presence of the MCSA on the cell surface does not signal malignant transformation per se. Rather, it appears to be associated with viral gene amplification that takes place in the thymus, the target organ for the leukemogenic process. Preleukemic cells are defined by the presence of MCSA in association with the Thy-1.2 marker.