Crucial role of FLT3 ligand in immune reconstitution following bone marrow transplantation and high dose chemotherapy.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/166280
- author
- Buza-Vidas, Natalija LU ; Cheng, Min LU ; Duarte, Sara LU ; NozadCharoudeh, Hojjatollah LU ; Jacobsen, Sten Eirik W LU and Sitnicka Quinn, Ewa LU
- organization
- publishing date
- 2007
- 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
- 2016-04-01 12:23:50
- date last changed
- 2022-04-05 21:49:34
@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}},
doi = {{10.1182/blood-2006-09-047480}},
volume = {{110}},
year = {{2007}},
}