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

Buza-Vidas, Natalija LU ; Cheng, Min LU ; Duarte, Sara LU ; NozadCharoudeh, Hojjatollah LU ; Jacobsen, Sten Eirik W LU and Sitnicka Quinn, Ewa LU (2007) In Blood 110(1). p.424-432
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
110
issue
1
pages
424 - 432
publisher
American Society of Hematology
external identifiers
  • wos:000247611000061
  • scopus:34347378240
ISSN
1528-0020
DOI
10.1182/blood-2006-09-047480
language
English
LU publication?
yes
id
33af6777-e20d-4a01-a1d2-5ce30d840fdb (old id 166280)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17379745&dopt=Abstract
date added to LUP
2007-07-23 16:05:58
date last changed
2017-07-30 03:49:34
@article{33af6777-e20d-4a01-a1d2-5ce30d840fdb,
  abstract     = {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.},
  author       = {Buza-Vidas, Natalija and Cheng, Min and Duarte, Sara and NozadCharoudeh, Hojjatollah and Jacobsen, Sten Eirik W and Sitnicka Quinn, Ewa},
  issn         = {1528-0020},
  language     = {eng},
  number       = {1},
  pages        = {424--432},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Crucial role of FLT3 ligand in immune reconstitution following bone marrow transplantation and high dose chemotherapy.},
  url          = {http://dx.doi.org/10.1182/blood-2006-09-047480},
  volume       = {110},
  year         = {2007},
}