RT Journal Article
SR Electronic
T1 A Mouse Carrying Genetic Defect in the Choice Between T and B Lymphocytes
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 4591
OP 4598
VO 161
IS 9
A1 Tokoro, Yayoi
A1 Sugawara, Takehiko
A1 Yaginuma, Hiroyuki
A1 Nakauchi, Hiromitsu
A1 Terhorst, Cox
A1 Wang, Baoping
A1 Takahama, Yousuke
YR 1998
UL http://www.jimmunol.org/content/161/9/4591.abstract
AB Transgenic 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.