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Blood, 1 July 2007, Vol. 110, No. 1, pp. 424-432.
Prepublished online as a Blood First Edition Paper on March 22, 2007; DOI 10.1182/blood-2006-09-047480.
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Submitted September 14, 2006
Accepted March 9, 2007
Crucial role of FLT3 ligand in immune reconstitution following bone marrow transplantation and high dose chemotherapy
Natalija Buza-Vidas, Min Cheng, Sara Duarte, Hojjatollah Nozad, Sten Eirik W Jacobsen*, and Ewa Sitnicka
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology & Cell Therapy, Lund University, Lund, Sweden
* Corresponding author; email: sten.jacobsen{at}med.lu.se.
Almost five decades after the first clinical transplantations, delayed immune reconstitution remains a considerable hurdle in bone marrow (BM) transplantation, and the mechanisms regulating immune reconstitution post-transplantation remain to be established. Whereas adult fms-like tyrosine kinase 3 ligand deficient (FL-/-) mice have reduced numbers of early B and T cell progenitors, they sustain close to normal levels of mature B and T cells. Herein, we demonstrate that adult BM cells fail to reconstitute B cell progenitors and conventional B cells in lethally irradiated FL-/- recipients, which also display delayed kinetics of T cell reconstitution. Similarly, FL is essential for B cell regeneration following chemotherapy-induced myeloablation. In contrast, fetal progenitors reconstitute B lymphopoiesis in FL-/- mice albeit at reduced levels. A critical role of FL in adult B lymphopoiesis is further substantiated by an age-progressive decline in peripheral conventional B cells in FL-/- mice, whereas fetally and early postnatally derived B1 and marginal zone B cells are sustained in a FL-independent manner. Thus, FL plays a crucial role in sustaining conventional B lymphopoiesis in adult mice, and as a consequence, our finding implicate a critical role of FL in promoting immune reconstitution following myeloablation and BM transplantation.

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