Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo.
Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.
Hozumi
Katsuto
K
Department of Immunology, and Center for Embryogenesis and Organogenesis, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Negishi
Naoko
N
Suzuki
Daisuke
D
Abe
Natsumi
N
Sotomaru
Yusuke
Y
Tamaoki
Norikazu
N
Mailhos
Carolina
C
Ish-Horowicz
David
D
Habu
Sonoko
S
Owen
Michael J
MJ
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein