title: Mesenchymal stromal cells protect against caspase 3-mediated apoptosis of CD19(+) peripheral B cells through contact-dependent upregulation of VEGF.
abstract: The immune suppressive and anti-inflammatory capabilities of bone marrow-derived mesenchymal stromal cells (MSCs) represent an innovative new tool in regenerative medicine and immune regulation. The potent immune suppressive ability of MSC over T cells, dendritic cells, and natural killer cells has been extensively characterized, however, the effect of MSC on B cell function has not yet been clarified. In this study, the direct effect of MSC on peripheral blood B cell function is defined and the mechanism utilized by MSC in enhancing B cell survival in vitro identified. Human MSC supported the activation, proliferation, and survival of purified CD19(+) B cells through a cell contact-dependent mechanism. These effects were not mediated through B cell activating factor or notch signaling. However, cell contact between MSC and B cells resulted in increased production of vascular endothelial growth factor (VEGF) by MSC facilitating AKT phosphorylation within the B cell and inhibiting caspase 3-mediated apoptosis. Blocking studies demonstrated that this cell contact-dependent effect was not dependent on signaling through CXCR4-CXCL12 or through the epidermal growth factor receptor (EGFR). These results suggest that direct cell contact between MSC and B cells supports B cell viability and function, suggesting that MSC may not represent a suitable therapy for B cell-mediated disease.
authors.affiliation: Institute of Immunology, Maynooth University, National University of Ireland Maynooth , Maynooth, Ireland .
authors.forename: Marc E
authors.initials: ME
authors.lastname: Healy
authors.affiliation: Institute of Immunology, Maynooth University, National University of Ireland Maynooth , Maynooth, Ireland .
authors.forename: Ronan
authors.initials: R
authors.lastname: Bergin
authors.affiliation: Institute of Immunology, Maynooth University, National University of Ireland Maynooth , Maynooth, Ireland .
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Mahon
authors.affiliation: Institute of Immunology, Maynooth University, National University of Ireland Maynooth , Maynooth, Ireland .
authors.forename: Karen
authors.initials: K
authors.lastname: English
mesh_terms: D018941:Antigens, CD19 / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D053148:Caspase 3 / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology; D015533:Transcriptional Activation / Q000276:immunology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D018941:Antigens, CD19; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C505407:CASP3 protein, human; D053148:Caspase 3