Function of Jam‐B/Jam‐C Interaction in Homing and Mobilization of Human and Mouse Hematopoietic Stem and Progenitor Cells

The junctional adhesion molecules Jam‐b and Jam‐c interact together at interendothelial junctions and have been involved in the regulation of immune response, inflammation, and leukocyte migration. More recently, Jam‐c has been found to be expressed by hematopoietic stem and progenitor cells (HSPC) in mouse. Conversely, we have reported that Jam‐b is present on bone marrow stromal cells and that Jam‐b ‐deficient mice have defects in the regulation of hematopoietic stem cell pool. In this study, we have addressed whether interaction between Jam‐b and Jam‐c participates to HSPC mobilization or hematopoietic reconstitution after irradiation. We show that a blocking monoclonal antibody directed against Jam‐c inhibits hematopoietic reconstitution, progenitor homing to the bone marrow, and induces HSPC mobilization in a Jam‐b dependent manner. In the latter setting, antibody treatment over a period of 3 days does not alter hematopoietic differentiation nor induce leukocytosis. Results are translated to human hematopoietic system in which a functional adhesive interaction between JAM‐B and JAM‐C is found between human HSPC and mesenchymal stem cells. Such an interaction does not occur between HSPC and human endothelial cells or osteoblasts. It is further shown that anti‐JAM‐C blocking antibody interferes with CD34 + hematopoietic progenitor homing in mouse bone marrow suggesting that monoclonal antibodies inhibiting JAM‐B/JAM‐C interaction may represent valuable therapeutic tools to improve stem cell mobilization protocols. S tem C ells 2014;32:1043–1054