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Crucial role of FLT3 ligand in immune reconstitution following bone marrow transplantation and high dose chemotherapy.

På svenska

Author

  • Natalija Buza-Vidas
  • Min Cheng
  • Sara Duarte
  • Hojjatollah NozadCharoudeh
  • Sten Eirik W Jacobsen
  • Ewa Sitnicka Quinn

Summary, in English

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 Band 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.

Publishing year

2007

Language

English

Pages

424-432

Publication/Series

Blood

Volume

110

Issue

1

Document type

Journal article

Publisher

American Society of Hematology

Topic

  • Hematology

Status

Published

Research group

  • Lymphoid Development and Regulation

ISBN/ISSN/Other

  • ISSN: 1528-0020