A mouse carrying genetic defect in the choice between T and B lymphocytes

Transgenic mice with human CD3 epsilon gene have been shown to exhibit early arrest of T cell development in the thymus, The present study shows that, instead of T cells, B cells are generated in the thymus of a line, tg epsilon 26, of the human CD3 epsilon transgenic mice. The accumulation of mature B cells in the thymus was found only in tge26 mice, not in other human CD3 epsilon transgenic mouse lines or other T cell-deficient mice, including CD3-epsilon knockout mice and TCR-beta/TCR-delta double knockout mice. Hanging drop-mediated transfer into 2-deoxyguanosine-treated thymus lobes showed that lymphoid progenitor cells rather than thymus stromal cells were responsible for abnormal B cell development in tg epsilon 26 thymus, and that tg epsilon 26 fetal liver cells were destined to become B cells in normal thymus even in the presence of normal progenitor cells undergoing T cell development. These results indicate that lymphoid progenitor cells in tg epsilon 26 mice are genetically defective in thymic choice between T cells and B cells, generating B cells even in normal thymus environment. Interestingly, tg epsilon 26 thymocytes expressed GATA-3 and TCF-1, but not LEF-1 and PEBP-2 alpha, among T cell-specific transcription factors that are involved ih early T cell development, indicating that GATA-3 and TCF-1 expressed during thymocyte development do not necessarily determine the cell fate into T cell lineage. Thus, tg epsilon 26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective.