Delta-like 1 is essential for the maintenance of marginal zone B cells in normal mice but not in autoimmune mice.
Notch2 and Delta-like 1 (Dll1) have been implicated in the development of marginal zone B (MZB) cells. In the present study, we characterized the expression and function of mouse Notch receptors and ligands in the spleen by using newly generated mAbs. Although Notch2 was expressed on both B and T cells in the spleen, the highest expression was observed on precursors of marginal zone B and MZB cells. Dll1 was expressed on macrophage and erythroblasts in the red pulp, but not on B cells or marginal zone macrophage. Administration of a blocking mAb against Dll1 not only blocked the development of MZB cells in juvenile mice but also gradually depleted the pre-established MZB cells in adult mice, indicating a critical role for Dll1 in the maintenance of MZB cells in the spleen of normal mice. Interestingly, Dll1 was not necessary for the maintenance of MZB cells in lupus-prone (NZB x NZW) F1 mice particularly after the onset of the disease, suggesting that the Dll1 independence may be a feature of dysregulated MZB cells producing auto-antibodies.
Moriyama
Yuko
Y
Department of Immunology, Biomedical Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. mori-yu@med.juntendo.ac.jp
Sekine
Chiyoko
C
Koyanagi
Akemi
A
Koyama
Noriko
N
Ogata
Hideko
H
Chiba
Shigeru
S
Hirose
Sachiko
S
Okumura
Ko
K
Yagita
Hideo
H
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008814:Mice, Inbred NZB; D051883:Receptor, Notch2 / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D019138:Antibodies, Blocking; D001323:Autoantibodies; C511877:Dll3 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051883:Receptor, Notch2