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Reduced EBF expression underlies loss of B cell potential of hematopoietic progenitors with age.

Abstract : Summary 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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Contributor : Marie-Christine Vougny Connect in order to contact the contributor
Submitted on : Friday, May 7, 2010 - 3:23:24 PM
Last modification on : Thursday, April 7, 2022 - 10:10:20 AM

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Chloé Lescale, Sheila Dias, Jérôme Maës, Ana Cumano, Paul Szabo, et al.. Reduced EBF expression underlies loss of B cell potential of hematopoietic progenitors with age.. Aging Cell, Wiley Open Access, 2010, epub ahead of print. ⟨10.1111/j.1474-9726.2010.00566.x⟩. ⟨pasteur-00481906⟩



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