A mouse carrying genetic defect in the choice between T and B lymphocytes.
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.
Tokoro
Y
Y
Department of Immunology, University of Tsukuba, Tennodai, Japan.
Sugawara
T
T
Yaginuma
H
H
Nakauchi
H
H
Terhorst
C
C
Wang
B
B
Takahama
Y
Y
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000473:pathology*; D017252:CD3 Complex; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006410:Hematopoiesis / Q000235:genetics*; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000473:pathology*; D008099:Liver / Q000196:embryology / Q000473:pathology; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000172:deficiency / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics; D051822:T Cell Transcription Factor 1; D013950:Thymus Gland / Q000473:pathology*; D015534:Trans-Activators / Q000096:biosynthesis; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
D017252:CD3 Complex; C115335:CD3E protein, human; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors