Notch 1-deficient common lymphoid precursors adopt a B cell fate in the thymus.
We have recently reported that Notch 1, a member of the Notch multigene family, is essential for the development of murine T cells. Using a mouse model in which Notch 1 is inactivated in bone marrow (BM) precursors we have shown that B cells instead of T cells are found in the thymus of BM chimeras. However, it is not clear whether these B cells develop by default from a common lymphoid precursor due to the absence of Notch 1 signaling, or whether they arise as a result of perturbed migration of BM-derived B cells and/or altered homeostasis of normal resident thymic B cells. In this report we show that Notch 1-deficient thymic B cells resemble BM B cells in phenotype and turnover kinetics and are located predominantly in the medulla and corticomedullary junction. Peripheral blood lymphocyte analysis shows no evidence of recirculating Notch1(-/)- BM B cells. Furthermore, lack of T cell development is not due to a failure of Notch1(-/)- precursors to home to the thymus, as even after intrathymic reconstitution with BM cells, B cells instead of T cells develop from Notch 1-deficient precursors. Taken together, these results provide evidence for de novo ectopic B cell development in the thymus, and support the hypothesis that in the absence of Notch 1 common lymphoid precursors adopt the default cell fate and develop into B cells instead.
Wilson
A
A
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
MacDonald
H R
HR
Radtke
F
F
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002465:Cell Movement; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors
D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors