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.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11581321
Keywords: Animals ; B-Lymphocytes/*cytology ; Bone Marrow Cells ; Cell Differentiation ; Cell Movement ; Hematopoietic Stem Cells/*cytology ; Membrane Proteins/*deficiency ; Mice ; Mice ; Inbred C57BL ; Mice ; Mutant Strains ; Receptor ; Notch1 ; *Receptors ; Cell Surface ; Research Support ; Non-U.S. Gov't ; Signal Transduction ; T-Lymphocytes/cytology ; Thymus Gland/*cytology ; *Transcription Factors
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 1066 Epalinges, Switzerland.
Record created on 2006-12-05, modified on 2016-08-08