Bootcongres

Background: Mesenchymal stem cells (MSC) have proven immunomodulatory capacity which makes them a promising therapeutic tool in transplantation. While the immunosuppressive effect of MSC on T cell-mediated effector mechanisms has been well studied, less is known about the effects of MSC on B cell-mediated immune responses. 

Methods: MSC were isolated from subcutaneous fat tissue from kidney transplant donors. Resting mature B cells from tonsils were obtained by CD43 negative selection with Magnetic Activated Cell Sorting (MACS). MSC were co-cultured with CFSE-labeled B cells stimulated in a T cell-like fashion (anti-IgM + anti-CD40 + IL2) or by PMA/ionomycin activated CD4 T cells. Proliferation and B cell phenotype were analyzed by Flow Cytometry, and IgG production quantified by ELISA.

Results: Proliferation of B cells activated in a T cells-like manner (anti-IgM + anti-CD40 + IL2) was not affected by the presence of MSC, while MSC decrease the proliferation of B cells stimulated with activated T cells. An induction of plasmablasts (CD19⁺ CD27^high CD38^high)occurred when B cells were stimulated in a T cell dependent manner or in the presence of activated CD4 T cells. MSC abolished the differentiation into plasmablasts completely, which was correlated with decreased IgG production.

Furthermore, MSCs induced an increase in the percentage of CD19⁺ CD27^- CD38^high CD24^high regulatory-like B cells when stimulated in a Tcell-like fashion. 

Conclusion: MSC inhibit B cell differentiation while increasing the proportion of regulatory-like B cells. The reduction of B cell proliferation by MSC is T cell-dependent. These results suggest a therapeutic role of MSC for the treatment of patients suffering from B cell mediated alloreactivity.