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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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TRANSPLANTATION

Crucial role of FLT3 ligand in immune reconstitution after bone marrow transplantation and high-dose chemotherapy

Natalija Buza-Vidas1, Min Cheng1, Sara Duarte1, Hojjatollah Nozad1, Sten Eirik W. Jacobsen1, and Ewa Sitnicka1

1 Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Sweden

Almost 5 decades after the first clinical transplantations, delayed immune reconstitution remains a considerable hurdle in bone marrow transplantation, and the mechanisms regulating immune reconstitution after 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 bone marrow 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 after 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 findings implicate a critical role of FL in promoting immune reconstitution after myeloablation and bone marrow transplantation.


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Intrathymic expression of Flt3 ligand enhances thymic recovery after irradiation
J. Exp. Med., March 17, 2008; 205(3): 523 - 531.
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