International Immunology Advance Access originally published online on April 1, 2008
International Immunology 2008 20(6):763-773; doi:10.1093/intimm/dxn034
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Delta-like 1 is essential for the maintenance of marginal zone B cells in normal mice but not in autoimmune mice
1 Department of Immunology
2 Division of Cell Biology, Biomedical Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
3 Department of Cell Therapy and Transplantation Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
4 Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Correspondence to: Y. Moriyama; E-mail: mori-yu{at}med.juntendo.ac.jp or H. Yagita; E-mail: hyagita{at}med.juntendo.ac.jp
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.
Keywords: autoimmunity, Delta-like 1, marginal zone B cells, Notch2
Transmitting editor: T. Watanabe
Received 10 January 2008, accepted 6 March 2008.
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