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Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging

ABSTRACT Within the bone marrow, the endosteal niche plays a crucial role in B‐cell differentiation. Because spaceflight is associated with osteoporosis, we investigated whether changes in bone microstructure induced by a ground‐based model of spaceflight, hind limb unloading (HU), could affect B ly...

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Published in:The FASEB journal 2015-02, Vol.29 (2), p.455-463
Main Authors: Lescale, Chloe, Schenten, Veronique, Djeghloul, Dounia, Bennabi, Meriem, Gaignier, Fanny, Vandamme, Katleen, Strazielle, Catherine, Kuzniak, Isabelle, Petite, Herve, Dosquet, Christine, Frippiat, Jean‐Pol, Goodhardt, Michele
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cited_by cdi_FETCH-LOGICAL-c4730-ba6651b3d51d8c2910d64f4f784e43b560ae8093f6db59aec62d2f0c4263e7d53
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creator Lescale, Chloe
Schenten, Veronique
Djeghloul, Dounia
Bennabi, Meriem
Gaignier, Fanny
Vandamme, Katleen
Strazielle, Catherine
Kuzniak, Isabelle
Petite, Herve
Dosquet, Christine
Frippiat, Jean‐Pol
Goodhardt, Michele
description ABSTRACT Within the bone marrow, the endosteal niche plays a crucial role in B‐cell differentiation. Because spaceflight is associated with osteoporosis, we investigated whether changes in bone microstructure induced by a ground‐based model of spaceflight, hind limb unloading (HU), could affect B lymphopoiesis. To this end, we analyzed both bone parameters and the frequency of early hematopoietic precursors and cells of the B lineage after 3, 6, 13, and 21 d of HU. We found that limb disuse leads to a decrease in both bone microstructure and the frequency of B‐cell progenitors in the bone marrow. Although multi‐potent hematopoietic progenitors were not affected by HU, a decrease in B lymphopoiesis was observed as of the common lymphoid progenitor (CLP) stage with a major block at the progenitor B (pro‐B) to precursor B (pre‐B) cell transition (5‐ to 10‐fold decrease). The modifications in B lymphopoiesis were similar to those observed in aged mice and, as with aging, decreased B‐cell generation in HU mice was associated with reduced expression of B‐cell transcription factors, early B‐cell factor (EBF) and Pax5, and an alteration in STAT5‐mediated IL‐7 signaling. These findings demonstrate that mechanical unloading of hind limbs results in a decrease in early B‐cell differentiation resembling age‐related modifications in B lymphopoiesis.—Lescale, C., Schenten, V., Djeghloul, D., Bennabi, M., Gaignier, F., Vandamme, K., Strazielle, C., Kuzniak, I., Petite, H., Dosquet, C., Frippiat, J.‐P., Goodhardt, M. Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging. FASEB J. 29, 455‐463 (2015). www.fasebj.org
doi_str_mv 10.1096/fj.14-259770
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The modifications in B lymphopoiesis were similar to those observed in aged mice and, as with aging, decreased B‐cell generation in HU mice was associated with reduced expression of B‐cell transcription factors, early B‐cell factor (EBF) and Pax5, and an alteration in STAT5‐mediated IL‐7 signaling. These findings demonstrate that mechanical unloading of hind limbs results in a decrease in early B‐cell differentiation resembling age‐related modifications in B lymphopoiesis.—Lescale, C., Schenten, V., Djeghloul, D., Bennabi, M., Gaignier, F., Vandamme, K., Strazielle, C., Kuzniak, I., Petite, H., Dosquet, C., Frippiat, J.‐P., Goodhardt, M. Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging. 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subjects Adrenal Cortex Hormones - metabolism
Aging
Animals
B-Lymphocytes - cytology
Bone Marrow Cells - cytology
Bone Remodeling
B‐cell differentiation
Cell Differentiation
Cell Lineage
Cytokines - metabolism
gravity
Hematopoietic Stem Cells - cytology
Hindlimb Suspension - physiology
Immunoglobulins - metabolism
Immunology
immunosenescence
Interleukin-7 - metabolism
Life Sciences
Lymphopoiesis - physiology
Mice
Mice, Inbred C57BL
Microbiology and Parasitology
Models, Animal
PAX5 Transcription Factor - metabolism
Space Flight
STAT5 Transcription Factor - metabolism
Stem Cells
Time Factors
Trans-Activators - metabolism
X-Ray Microtomography
title Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging
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