Bone Marrow Endothelial Cells Induce Immature and Mature B Cell Egress in Response to Erythropoietin

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    • Ito Takeshi Ito Takeshi
    • Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University|Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University
    • Hamazaki Yoko Hamazaki Yoko
    • Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University|Center for iPS Cell Research and Application (CiRA), Laboratory of Immunobiology, Graduate School of Medicine, Kyoto University


<p>Bone marrow stromal cells, including endothelial cells and mesenchymal stromal cells, support the maintenance, differentiation, and retention of hematopoietic stem and precursor cells under steady state conditions. At the onset of an emergency, such as severe blood loss or infection, the status of hematopoiesis in the bone marrow changes rapidly to ensure efficient production of cells of specific lineages; however, the function of stromal cells in emergency hematopoiesis has not been fully elucidated. Here, we unexpectedly found that B precursor, mature B, and T cells were released from the bone marrow into the blood circulation in the early phase of hemorrhagic anemia and phenylhydrazine-induced hemolytic anemia. Administration of erythropoietin, which normally increases in response to anemia, stimulated the egress of IgD<sup>low</sup> immature B cells and recirculating mature B cells, which usually reside in the perivascular and intravascular space, from the bone marrow within 24 h. We also observed that endothelial cells in the bone marrow expressed erythropoietin receptor, and the expression levels were higher than those in other tissues. Erythropoietin stimulation of bone marrow endothelial cells induced the phosphorylation of STAT5 <i>in vitro</i>. Moreover, <i>in vivo</i> treatment with erythropoietin decreased surface VCAM1 expression and <i>Cxcl12</i> transcription in bone marrow endothelial cells, both of which are essential for immature and mature B cell retention in the bone marrow. These results suggest that bone marrow endothelial cells can sense and rapidly respond to erythropoietin increase during anemia, thereby regulating B cell emigration from the bone marrow during emergency hematopoiesis.</p><p>Key words: erythropoietin, anemia, endothelial cells, B cell, bone marrow microenvironment</p>


  • Cell Structure and Function

    Cell Structure and Function 42(2), 149-157, 2017

    Japan Society for Cell Biology


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