MCB Accepts, published online ahead of print on 8 January 2007

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Mol. Cell. Biol. doi:10.1128/MCB.01402-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The Bloom's syndrome helicase is critical for development and function of the T cell lineage

Holger Babbe, Nicholas Chester, Philip Leder, and Boris Reizis^*

Department of Genetics, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, MA 02115, USA; Department of Microbiology, Columbia University Medical Center, 701 W 168th St., New York, NY 10032, USA

^* To whom correspondence should be addressed. Email: bvr2101{at}columbia.edu.

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 -selection checkpoint that was partially p53-dependent. Blm-deficient thymocytes rearranged their T cell receptor (TCR)- 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.

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]