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© Research
Publication : Aging cell

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Aging cell - 13 Mar 2010

Lescale C, Dias S, Maës J, Cumano A, Szabo P, Charron D, Weksler ME, Dosquet C, Vieira P, Goodhardt M

Link to Pubmed [PMID] – 20331442

Aging Cell 2010 Jun;9(3):410-9

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.