Journal
AGING CELL
Volume 9, Issue 3, Pages 410-419Publisher
WILEY
DOI: 10.1111/j.1474-9726.2010.00566.x
Keywords
aging; B cells; EBF; hematopoietic progenitors; STAT5
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Funding
- Institut National de la Sante et de la Recherche Medicale
- Institut Pasteur
- Fondation pour la Recherche Medicale, INSERM AIP Adult Stem Cells [ASE04145DSA, AMA03022DSA]
- NIH [R-01 AG-021033]
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P>Aging is accompanied by a reduction in the generation of B lymphocytes leading to impaired immune responses. In this study, we have investigated whether the decline in B lymphopoiesis is due to age-related defects in the hematopoietic stem cell compartment. The ability of hematopoietic stem cells from old mice to generate B cells, as measured in vitro, is decreased 2-5-fold, while myeloid potential remains unchanged. This age-related decrease in B-cell potential is more marked in common lymphoid progenitors (CLP) and was associated with reduced expression of the B-lineage specifying factors, EBF and Pax5. Notably, retrovirus-mediated expression of EBF complemented the age-related loss of B-cell potential in CLP isolated from old mice. Furthermore, transduction of CLP from old mice with a constitutively active form of STAT5 restored both EBF and Pax5 expression and increased B-cell potential. These results are consistent with a mechanism, whereby reduced expression of EBF with age decreases the frequency with which multipotent hematopoietic progenitors commit to a B-cell fate, without altering their potential to generate myeloid cells.
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