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

• Published in: The Journal of immunology (1950) 1998-11, Vol.161 (9), p.4591-4598
• Main Authors: Tokoro, Yayoi, Sugawara, Takehiko, Yaginuma, Hiroyuki, Nakauchi, Hiromitsu, Terhorst, Cox, Wang, Baoping, Takahama, Yousuke
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; B-Lymphocytes - pathology; CD3 Complex; Cell Differentiation; Cell Lineage - genetics; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; GATA3 Transcription Factor; Gene Expression Regulation, Developmental; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Hematopoiesis - genetics; Hepatocyte Nuclear Factor 1-alpha; Humans; Immunologic Deficiency Syndromes - immunology; Immunologic Deficiency Syndromes - pathology; Liver - embryology; Liver - pathology; Lymphoid Enhancer-Binding Factor 1; Mice; Mice, Knockout; Mice, Transgenic - genetics; Mice, Transgenic - immunology; Organ Culture Techniques; Polymerase Chain Reaction; Receptors, Antigen, T-Cell - deficiency; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - physiology; Receptors, Antigen, T-Cell, alpha-beta - deficiency; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, gamma-delta - deficiency; Receptors, Antigen, T-Cell, gamma-delta - genetics; T Cell Transcription Factor 1; Thymus Gland - pathology; Trans-Activators - biosynthesis; Transcription Factor AP-2; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - metabolism; Transgenes
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.161.9.4591

Transgenic mice with human CD3epsilon 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 epsilon26, of the human CD3epsilon transgenic mice. The accumulation of mature B cells in the thymus was found only in tg epsilon26 mice, not in other human CD3epsilon 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 epsilon26 thymus, and that tg epsilon26 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 epsilon26 mice are genetically defective in thymic choice between T cells and B cells, generating B cells even in normal thymus environment. Interestingly, tg epsilon26 thymocytes expressed GATA-3 and TCF-1, but not LEF-1 and PEBP-2alpha, 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, tg epsilon26 mice provide a novel mouse model in that lineage choice between T and B lymphocytes is genetically defective.