Human mesenchymal stem cells modulate B-cell functions.
Human mesenchymal stem cells (hMSCs) suppress T-cell and dendritic-cell function and represent a promising strategy for cell therapy of autoimmune diseases. Nevertheless, no information is currently available on the effects of hMSCs on B cells, which may have a large impact on the clinical use of these cells. hMSCs isolated from the bone marrow and B cells purified from the peripheral blood of healthy donors were cocultured with different B-cell tropic stimuli. B-cell proliferation was inhibited by hMSCs through an arrest in the G0/G1 phase of the cell cycle and not through the induction of apoptosis. A major mechanism of B-cell suppression was hMSC production of soluble factors, as indicated by transwell experiments. hMSCs inhibited B-cell differentiation because IgM, IgG, and IgA production was significantly impaired. CXCR4, CXCR5, and CCR7 B-cell expression, as well as chemotaxis to CXCL12, the CXCR4 ligand, and CXCL13, the CXCR5 ligand, were significantly down-regulated by hMSCs, suggesting that these cells affect chemotactic properties of B cells. B-cell costimulatory molecule expression and cytokine production were unaffected by hMSCs. These results further support the potential therapeutic use of hMSCs in immune-mediated disorders, including those in which B cells play a major role.
Corcione
Anna
A
Laboratory of Oncology, G. Gaslini Institute, Largo G. Gaslini 5, 16148 Genova, Italy. annacorcione@ospedale-gaslini.ge.it
Benvenuto
Federica
F
Ferretti
Elisa
E
Giunti
Debora
D
Cappiello
Valentina
V
Cazzanti
Francesco
F
Risso
Marco
M
Gualandi
Francesca
F
Mancardi
Giovanni Luigi
GL
Pistoia
Vito
V
Uccelli
Antonio
A
D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001685:Biological Factors / Q000378:metabolism / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics; D002633:Chemotaxis; D018920:Coculture Techniques; D005786:Gene Expression Regulation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D016192:Resting Phase, Cell Cycle
D001685:Biological Factors; D018925:Chemokines