Date: Tuesday, June 14, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
The immunomodulatory capacity of mesenchymal stem cells (MSC) makes them a promising therapeutic tool in transplantation. MSC are recently gaining interest for their immunomodulatory effects on B cells. Here we explore the effect of inflammatory conditions on the interactions between MSC and B cells.
MSC were isolated from adipose tissue from kidney transplant donors and pre-treated with IFNγ for 72h (MSC-IFNγ). Mature B cells from spleens were obtained by CD43– selection with magnetic activated cell sorting. MSC were co-cultured with CFSE-labeled B cells and stimulated with anti-IgM+anti-CD40+IL2. Proliferation and B cell phenotype were analyzed by Flow Cytometry, and IL-10 and TNFα production quantified by ELISA.
Proliferation of activated naïve B cells (CD19+IgD+CD27–) was not affected by MSC but proliferation of memory B cells (switched: [CD19+IgD–CD27+] and non-switched: [CD19+IgD+CD27+]) was significantly reduced. MSC increased the percentage of naïve B cells and regulatory B cells (CD19+CD24hiCD38hi) characterized by IL-10 production
|Naive||Non-switched memory||Switched memory||Plasmablasts||Bregs|
MSC-IFNγ became strongly anti-proliferative, completely inhibiting non-switched memory B cell proliferation and partially reducing proliferation of naive and switched memory B cells.
However, MSC-IFNγ increased the ratio effector/regulatory B cell subsets compared to control MSC (B+: 21.3, B++MSC: 1.4, B++MSC-IFNγ: 8.7) which was correlated with lower IL-10/TNFα ratios (B+: 0.03, B++MSC: 3.3, B++MSC-IFNγ: 0.2).
MSC induce a pro-tolerogenic milieu reducing effector B cell proliferation and differentiation while increasing the proportion of Bregs.
Under inflammatory conditions MSC become more anti-proliferative but lose their regulatory B cell inducing capacity, allowing them to intervene in ongoing B cell responses.
These results are important to take into consideration for the design of a clinical trial with MSC.
CITATION INFORMATION: Franquesa M, Luk F, Korevaar S, Boon L, Borras F, Betjes M, Baan C, Hoogduijn M. Inflammatory Conditions Switch the Effect of MSC on B Cells from Pro-Tolerogenic to Anti-Proliferative. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Franquesa M, Luk F, Korevaar S, Boon L, Borras F, Betjes M, Baan C, Hoogduijn M. Inflammatory Conditions Switch the Effect of MSC on B Cells from Pro-Tolerogenic to Anti-Proliferative. [abstract]. Am J Transplant. 2016; 16 (suppl 3). http://atcmeetingabstracts.com/abstract/inflammatory-conditions-switch-the-effect-of-msc-on-b-cells-from-pro-tolerogenic-to-anti-proliferative/. Accessed September 21, 2017.
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