A Mouse Carrying Genetic Defect in the Choice Between T and B Lymphocytes

Abstract

AbstractTransgenic mice with human CD3ε 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, tgε26, of the human CD3ε transgenic mice. The accumulation of mature B cells in the thymus was found only in tgε26 mice, not in other human CD3ε transgenic mouse lines or other T cell-deficient mice, including CD3-ε knockout mice and TCR-β/TCR-δ 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 tgε26 thymus, and that tgε26 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 tgε26 mice are genetically defective in thymic choice between T cells and B cells, generating B cells even in normal thymus environment. Interestingly, tgε26 thymocytes expressed GATA-3 and TCF-1, but not LEF-1 and PEBP-2α, among T cell-specific transcription factors that are involved in 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, tgε26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective.