B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2

Winkler, IG; Bendall, LJ; Forristal, CE; Helwani, F; Nowlan, B; Barbier, V; Shen, Y; Cisterne, A; Sedger, LM; Levesque, JP

B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2

Winkler, IG Bendall, LJ Forristal, CE Helwani, F Nowlan, B Barbier, V Shen, Y Cisterne, A Sedger, LM

Levesque, JP

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Publication Type:: Journal Article
Citation:: Haematologica, 2013, 98 (3), pp. 325 - 333
Issue Date:: 2013-01-01

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Field	Value	Language
dc.contributor.author	Winkler, IG	en_US
dc.contributor.author	Bendall, LJ	en_US
dc.contributor.author	Forristal, CE	en_US
dc.contributor.author	Helwani, F	en_US
dc.contributor.author	Nowlan, B	en_US
dc.contributor.author	Barbier, V	en_US
dc.contributor.author	Shen, Y	en_US
dc.contributor.author	Cisterne, A	en_US
dc.contributor.author	Sedger, LM https://orcid.org/0000-0003-1009-5683	en_US
dc.contributor.author	Levesque, JP	en_US
dc.date.issued	2013-01-01	en_US
dc.identifier.citation	Haematologica, 2013, 98 (3), pp. 325 - 333	en_US
dc.identifier.issn	0390-6078	en_US
dc.identifier.uri	http://hdl.handle.net/10453/27619
dc.description.abstract	Osteoblasts are necessary to B lymphopoiesis and mobilizing doses of G-CSF or cyclophosphamide inhibit osteoblasts, whereas AMD3100/Plerixafor does not. However, the effect of these mobilizing agents on B lymphopoiesis has not been reported. Mice (wild-type, knocked-out for TNF-α and TRAIL, or over-expressing Bcl-2) were mobilized with G-CSF, cyclophosphamide, or AMD3100. Bone marrow, blood, spleen and lymph node content in B cells was measured. G-CSF stopped medullar B lymphopoiesis with concomitant loss of B-cell colony-forming units, pre-pro-B, pro-B, pre-B and mature B cells and increased B-cell apoptosis by an indirect mechanism. Overexpression of the anti-apoptotic protein Bcl2 in transgenic mice rescued B-cell colony forming units and pre-pro-B cells in the marrow, and prevented loss of all B cells in marrow, blood and spleen. Blockade of endogenous soluble TNF-α with Etanercept, or combined deletion of the TNF-α and TRAIL genes did not prevent B lymphopoiesis arrest in response to G-CSF. Unlike G-CSF, treatments with cyclophosphamide or AMD3100 did not suppress B lymphopoiesis but caused instead robust B-cell mobilization. G-CSF, cyclophosphamide and AMD3100 have distinct effects on B lymphopoiesis and B-cell mobilization with: 1) G-CSF inhibiting medullar B lymphopoiesis without mobilizing B cells in a mechanism distinct from the TNF-α-mediated loss of B lymphopoiesis observed during inflammation or viral infections; 2) CYP mobilizing B cells but blocking their maturation; and 3) AMD3100 mobilizing B cells without affecting B lymphopoiesis. These results suggest that blood mobilized with these three agents may have distinct immune properties. © 2013 Ferrata Storti Foundation.	en_US
dc.relation.ispartof	Haematologica	en_US
dc.relation.isbasedon	10.3324/haematol.2012.069260	en_US
dc.subject.classification	Immunology	en_US
dc.subject.mesh	Spleen	en_US
dc.subject.mesh	B-Lymphocyte Subsets	en_US
dc.subject.mesh	Bone Marrow	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Cyclophosphamide	en_US
dc.subject.mesh	Heterocyclic Compounds	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	Granulocyte Colony-Stimulating Factor	en_US
dc.subject.mesh	Proto-Oncogene Proteins c-bcl-2	en_US
dc.subject.mesh	Hematopoietic Stem Cell Mobilization	en_US
dc.subject.mesh	Lymphopoiesis	en_US
dc.subject.mesh	Gene Expression	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Precursor Cells, B-Lymphoid	en_US
dc.title	B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	98	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	98	en_US

Abstract:

Osteoblasts are necessary to B lymphopoiesis and mobilizing doses of G-CSF or cyclophosphamide inhibit osteoblasts, whereas AMD3100/Plerixafor does not. However, the effect of these mobilizing agents on B lymphopoiesis has not been reported. Mice (wild-type, knocked-out for TNF-α and TRAIL, or over-expressing Bcl-2) were mobilized with G-CSF, cyclophosphamide, or AMD3100. Bone marrow, blood, spleen and lymph node content in B cells was measured. G-CSF stopped medullar B lymphopoiesis with concomitant loss of B-cell colony-forming units, pre-pro-B, pro-B, pre-B and mature B cells and increased B-cell apoptosis by an indirect mechanism. Overexpression of the anti-apoptotic protein Bcl2 in transgenic mice rescued B-cell colony forming units and pre-pro-B cells in the marrow, and prevented loss of all B cells in marrow, blood and spleen. Blockade of endogenous soluble TNF-α with Etanercept, or combined deletion of the TNF-α and TRAIL genes did not prevent B lymphopoiesis arrest in response to G-CSF. Unlike G-CSF, treatments with cyclophosphamide or AMD3100 did not suppress B lymphopoiesis but caused instead robust B-cell mobilization. G-CSF, cyclophosphamide and AMD3100 have distinct effects on B lymphopoiesis and B-cell mobilization with: 1) G-CSF inhibiting medullar B lymphopoiesis without mobilizing B cells in a mechanism distinct from the TNF-α-mediated loss of B lymphopoiesis observed during inflammation or viral infections; 2) CYP mobilizing B cells but blocking their maturation; and 3) AMD3100 mobilizing B cells without affecting B lymphopoiesis. These results suggest that blood mobilized with these three agents may have distinct immune properties. © 2013 Ferrata Storti Foundation.

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