This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Witt, C. M.
Right arrow Articles by Klug, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Witt, C. M.
Right arrow Articles by Klug, C. A.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2003, p. 8637-8650, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8637-8650.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Activated Notch2 Potentiates CD8 Lineage Maturation and Promotes the Selective Development of B1 B Cells

Colleen M. Witt,1 Vincent Hurez,2 C. Scott Swindle,1 Yoshio Hamada,3 and Christopher A. Klug1*

Division of Developmental and Clinical Immunology, Department of Microbiology,1 Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-3300,2 National Institute for Basic Biology, Okasaki, Japan3

Received 7 February 2003/ Returned for modification 10 April 2003/ Accepted 19 August 2003

Although studies have shown that the Notch2 family member is critical for embryonic development, little is known concerning its role in hematopoiesis. In this study, we show that the effects of an activated form of Notch2 (N2IC) on the T-cell lineage are dosage related. High-level expression of N2IC results in the development of T-cell leukemias. In contrast, lower-level expression of N2IC does not lead to transformation but skews thymocyte development to the CD8 lineage. Underlying this skew is a dramatic enhancement in positive selection and CD8SP maturation. N2IC permits early B-cell development but blocks the maturation of conventional B2 cells at the pre-B stage, which is the limit of endogenous Notch2 protein expression in developing B cells. Most strikingly, while B2 B cell development is blocked at the pre-B-cell stage, N2IC promotes the selective development of LPS-responsive B1 B cells. This study implicates a role for Notch2 in the maturation of the CD8 lineage and suggests a novel function for Notch2 in the development of the B1 B-cell subset.

* Corresponding author. Mailing address: Department of Microbiology, Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, WTI387 1824 6th Ave., Birmingham, Alabama 35294-3300. Phone: (205) 934-1424. Fax: (205) 934-1875. E-mail: chris.klug{at}ccc.uab.edu.

Molecular and Cellular Biology, December 2003, p. 8637-8650, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8637-8650.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Quillard, T., Coupel, S., Coulon, F., Fitau, J., Chatelais, M., Cuturi, M.C., Chiffoleau, E., Charreau, B. (2008). Impaired Notch4 Activity Elicits Endothelial Cell Activation and Apoptosis: Implication for Transplant Arteriosclerosis. Arterioscler. Thromb. Vasc. Bio. 28: 2258-2265 [Abstract] [Full Text]  
  • Troen, G., Wlodarska, I., Warsame, A., Hernandez Llodra, S., De Wolf-Peeters, C., Delabie, J. (2008). NOTCH2 mutations in marginal zone lymphoma. haematol 93: 1107-1109 [Full Text]  
  • Moriyama, Y., Sekine, C., Koyanagi, A., Koyama, N., Ogata, H., Chiba, S., Hirose, S., Okumura, K., Yagita, H. (2008). Delta-like 1 is essential for the maintenance of marginal zone B cells in normal mice but not in autoimmune mice. Int Immunol 20: 763-773 [Abstract] [Full Text]  
  • LeBrun, D., Baetz, T., Foster, C., Farmer, P., Sidhu, R., Guo, H., Harrison, K., Somogyi, R., Greller, L. D., Feilotter, H. (2008). Predicting Outcome in Follicular Lymphoma by Using Interactive Gene Pairs. Clin. Cancer Res. 14: 478-487 [Abstract] [Full Text]  
  • Maraver, A., Tadokoro, C. E., Badura, M. L., Shen, J., Serrano, M., Lafaille, J. J. (2007). Effect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cells. Blood 110: 3218-3225 [Abstract] [Full Text]  
  • Laky, K., Fowlkes, B.J. (2007). Presenilins regulate {alpha}{beta} T cell development by modulating TCR signaling. JEM 204: 2115-2129 [Abstract] [Full Text]  
  • Cheng, P., Nefedova, Y., Corzo, C. A., Gabrilovich, D. I. (2007). Regulation of dendritic-cell differentiation by bone marrow stroma via different Notch ligands. Blood 109: 507-515 [Abstract] [Full Text]  
  • Hardy, R. R. (2006). B-1 B cell development.. J. Immunol. 177: 2749-2754 [Abstract] [Full Text]  
  • Subramanian, S., Yim, Y.-S., Liu, K., Tus, K., Zhou, X. J., Wakeland, E. K. (2005). Epistatic Suppression of Systemic Lupus Erythematosus: Fine Mapping of Sles1 to Less Than 1 Mb. J. Immunol. 175: 1062-1072 [Abstract] [Full Text]  
  • de La Coste, A., Six, E., Fazilleau, N., Mascarell, L., Legrand, N., Mailhe, M.-P., Cumano, A., Laabi, Y., Freitas, A. A. (2005). In Vivo and in Absence of a Thymus, the Enforced Expression of the Notch Ligands Delta-1 or Delta-4 Promotes T Cell Development with Specific Unique Effects. J. Immunol. 174: 2730-2737 [Abstract] [Full Text]  
  • Spira, A., Beane, J., Pinto-Plata, V., Kadar, A., Liu, G., Shah, V., Celli, B., Brody, J. S. (2004). Gene Expression Profiling of Human Lung Tissue from Smokers with Severe Emphysema. Am. J. Respir. Cell Mol. Bio. 31: 601-610 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»