Expression of Delta-like 1 in the splenic non-hematopoietic cells is essential for marginal zone B cell development

The Notch ligand Delta-like 1 (Dll1) is critical for the generation of marginal zone (MZ) B cells in the spleen. However, the precise mechanism underlying the differentiation of MZB cells is unclear. To determine whether hematopoietic cells or non-hematopoietic cells Provides the Dll1-mediated signals to primitive hematopoietic cells, we transplanted lineage(-) c-kit* Sca-1* (KSL) bone marrow cells derived from wildtype (Dll1(+/+)) GFP-transgenic mice into lethally irradiated Dll1 conditional knockout (cKO) mice. After transplantation, we examined the kinetics of hematopoietic reconstitution and found that although the frequency of stem/progenitor subsets and of more mature lymphoid, myeloid, and erythroid lineages were normal, the donor-derived hematopoietic cells failed to differentiate into MZB cells. We further demonstrated that while the splenic stromal cells of wild-type mice expressed Dll1 molecule, the splenic stromal cells of recipient Dill cKO mice deleted the expression of Dill. These results suggesting that the expression of Dill in splenic non-hematopoietic stromal cells, but not hematopoietic cells, is essential for the development of MZB cells. (C) 2008 Elsevier B.V. All rights reserved.