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 wild-type (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 Dll1 cKO mice deleted the expression of Dll1. These results suggesting that the expression of Dll1 in splenic non-hematopoietic stromal cells, but not hematopoietic cells, is essential for the development of MZB cells.
Sheng
Yin
Y
Division of Hematopoiesis, Research Center for Regenerative Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Yahata
Takashi
T
Negishi
Naoko
N
Nakano
Yasuhiro
Y
Habu
Sonoko
S
Hozumi
Katsuto
K
Ando
Kiyoshi
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism
C511877:Dll3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins