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Molecular and Cellular Biology, March 2007, p. 1947-1959, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01402-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Bloom's Syndrome Helicase Is Critical for Development and Function of the {alpha}ß T-Cell Lineage{triangledown} ,{dagger}

Holger Babbe,1 Nicholas Chester,1 Philip Leder,1 and Boris Reizis2*

Department of Genetics, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, Massachusetts 02115,1 Department of Microbiology, Columbia University Medical Center, 701 W. 168th St., New York, New York 100322

Received 31 July 2006/ Returned for modification 8 October 2006/ Accepted 18 December 2006

Bloom's syndrome is a genetic disorder characterized by increased incidence of cancer and an immunodeficiency of unknown origin. The BLM gene mutated in Bloom's syndrome encodes a DNA helicase involved in the maintenance of genomic integrity. To explore the role of BLM in the immune system, we ablated murine Blm in the T-cell lineage. In the absence of Blm, thymocytes were severely reduced in numbers and displayed a developmental block at the ß-selection checkpoint that was partially p53 dependent. Blm-deficient thymocytes rearranged their T-cell receptor (TCR) ß genes normally yet failed to survive and proliferate in response to pre-TCR signaling. Furthermore, peripheral T cells were reduced in numbers, manifested defective homeostatic and TCR-induced proliferation, and produced extensive chromosomal damage. Finally, CD4+ and CD8+ T-cell responses were impaired upon antigen challenge. Thus, by ensuring genomic stability, Blm serves a vital role for development, maintenance, and function of T lymphocytes, suggesting a basis for the immune deficiency in Bloom's syndrome.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University Medical Center, 701 W. 168th St., New York, NY 10032. Phone: (212) 305-5793. Fax: (212) 305-1468. E-mail: bvr2101{at}columbia.edu.

{triangledown} Published ahead of print on 8 January 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2007, p. 1947-1959, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01402-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Babbe, H., McMenamin, J., Hobeika, E., Wang, J., Rodig, S. J., Reth, M., Leder, P. (2009). Genomic Instability Resulting from Blm Deficiency Compromises Development, Maintenance, and Function of the B Cell Lineage. J. Immunol. 182: 347-360 [Abstract] [Full Text]  


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