Abstract
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-1lo), 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-1lo B220+population in the primary thymomas had not rearranged TCRγ, TCRβ, or Igκ genes, but contained subpopulations that assembled Ig DJH or VDJH 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-1lo 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.
Highlights
The ability of the v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) to immortalize immature lymphoid cells from bone marrow and fetal liver has been useful for identifying and characterizing immature stages of B-cell development (Rosenberg and Witte, 1988; Alt et al, 1984)
Coexpression of B220 and Thy-1l on immature lymphocytes in primary thymomas induced by A-MuLV
We used two-color flow cytometry to determine whether cells in A-MuLV-induced thymomas coexpress Thy-11 and B220+
Summary
The ability of the v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) to immortalize immature lymphoid cells from bone marrow and fetal liver has been useful for identifying and characterizing immature stages of B-cell development (Rosenberg and Witte, 1988; Alt et al, 1984). A-MuLV transformed cell lines derived from fetal liver have rearranged only DJH segments, but unlike the DJ-f population obtained from marrow, are not blocked at this stage of development and continue assembling Igh genes so that _
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