Transformation of Undifferentiated Thy-1(lo) B220(+) Thymic Lymphoid Cells by the Abelson Murine Leukemia Virus

Intrathymic injection of the Abelson murine leukemia virus (A-MuLV) results in transformation of immature T and B lymphoid cells. In this report we demonstrate that the concentration of A-MuLV injected into murine thymi influences the selection of the transformation target. Thus, concentrated A-MuLV gives rise to Thy-1(+) B220(-) thymomas. In contrast, dilute virus induces B220(+) thymomas that also express low levels of Thy- 1 (Thy-1(lo)), a phenotype that is similar to marrow-derived progenitor B-lymphoid cells (pro-B cells) that are highly susceptible to A-MuLV transformation in vitro. However, rare B220(+) lymphoid cells isolated from normal adult thymi were not transformed by A-MuLV in vitro, while B220(+) cells isolated from bone marrow were highly susceptible to transformation by A-MuLV. The Thy-1(lo) B220(+)population in the primary thymomas had not rearranged TCRγ, TCRβ, or Igκ genes, but contained subpopulations that assembled Ig DJ(H) or VDJ(H) genes and were therefore similar to transformed pro- and pre-B cells obtained from A-MuLV infected fetal liver and adult bone marrow, respectively. However, unlike A-MuLV-transformed pro- and pre-B cells, many (40– 70%) of the Thy-1(lo) B220(+) transformed thymoma cells had not rearranged Igh genes, and therefore appear to represent undifferentiated lymphoid cells. We conclude that A-MuLV may transform an undifferentiated lymphoid target in the thymus.