A checkpoint in B-lymphopoiesis related to Notch resistance

► Delta-like 1 represses B-lymphopoiesis. ► Flt3+ Il7r+ B220+ Cd19+ cells generate B cells even in the presence of delta-like 1. ► They are present in the bone marrow and few in the thymus. ► The absence of them explains why the thymus does not support B-lymphopoiesis. While murine B- and T-lymphopoiesis require overlapping molecules, they occur in separate organs: the bone marrow (BM) and the thymus, respectively. The BM microenvironment is incapable of supporting T-lymphopoiesis because of insufficient interactions of Notch1 with delta-like ligand (Dll). Notch1/Dll interactions also play a role in the suppression of B-lymphopoiesis in the thymus. However, it is still unclear whether the Notch1/Dll interaction alone explains why the thymus does not support B-lymphopoiesis. In this study, we compared the precursor population colonizing the thymus with that in the BM by culturing them on stromal cells expressing abundant Dll1. We demonstrated that Flt3+ Il7r+ B220+ Cd19+ BM cells gave rise to B cells under this condition. We defined them as resistant to Dll1. In the thymus, Dll1-resistant cells were undetectable. This suggested that the absence of Dll1-resistant cells might explain the absence of B-lymphopoiesis in the thymus.