Notch 1–deficient common lymphoid precursors adopt a B cell fate in the thymus

A Wilson, HR MacDonald, F Radtke - The Journal of experimental …, 2001 - rupress.org
A Wilson, HR MacDonald, F Radtke
The Journal of experimental medicine, 2001rupress.org
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 …
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.
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