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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-10-3139.

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Submitted October 17, 2002
Accepted January 23, 2003

Pax5 determines B versus T cell fate and does not block early myeloid-lineage development

Claudiu V Cotta, Zheng Zhang, Hyung-Gyoon Kim, and Christopher A Klug*

Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
Division of Developmental and Clinical Immunology, University of Alabama at Birmingham, Birmingham, AL, USA

* Corresponding author; email: chris.klug{at}ccc.uab.edu.

Progenitor B cells deficient in Pax5 are developmentally multipotent, suggesting that Pax5 is necessary to maintain commitment to the B cell lineage. Commitment may be mediated, in part, by Pax5 repression of myeloid-specific genes. To determine whether Pax5 expression in multipotential cells is sufficient to restrict development to the B cell lineage in vivo, we enforced expression of Pax5 in hematopoietic stem cells using a retroviral vector. Peripheral blood analysis of all animals reconstituted with Pax5-expressing cells indicated that greater than 90 percent of Pax5-expressing cells were B220+ mature B cells that were not malignant. Further analysis showed that Pax5 completely blocked T lineage development in the thymus but did not inhibit myelopoiesis or NK cell development in bone marrow. These results implicate Pax5 as a critical regulator of B versus T cell developmental fate and suggest that Pax5 may promote commitment to the B cell lineage by mechanisms that are independent of myeloid gene repression.


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