Abnormal rearrangements of T-cell receptor genes occur in long-term cultured bone marrow cells of lpr/lpr mice

To search the abnormality in prethymic T-cell precursors in lpr/lpr(lpr) mice, rearrangement and expression of T-cell receptor (TcR) genes were investigated in long-term cultured bone marrow (LTBM) cells of lpr mice, in which the developmental steps of T-cell precursors may be better synchronized than those in bone marrow (BM) cells. Neither rearrangement nor expression of TCR γ and δ genes were detected in the LTBM cells from +/+ control mice, whereas some γ gene rearrangements were detected in those derived from lpr mice, irrespective of the genetic background. When BM cells or LTBM cells from lpr mice were transplanted into supralethally irradiated +/+ mice, the lpr-derived BM cells appeared earlier in the thymus of the recipient mice than +/+-derived BM cells and the recipients suffered from lethal wasting syndrome. In addition, the lpr-derived BM cells showed higher activity in colony-forming unit spleen (CFUs) than the +/+-derived BM cells. These results suggest that the T-cell progenitors in the BM of lpr mice may be different not only in quantity but also in quality from those of +/+ mice.