Inflammatory Conditions Switch the Effect of MSC on B Cells from Pro-Tolerogenic to Anti-Proliferative.
1Transplantation and Nephrology Lab, Internal Medicine, Erasmus MC, Rotterdam, Netherlands
2IVECAT, Nephrology Department, IGTP, Badalona, Spain
3Bioceros, Utrecht, Netherlands.
Meeting: 2016 American Transplant Congress
Abstract number: D43
Keywords: B cells, Inflammation, Stem cells, Tolerance
Session Information
Session Name: Poster Session D: Chimerism/Stem Cells, Cellular/Islet Transplantation, Innate Immunity, Chronic Rejection
Session Type: Poster Session
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 | |
| B+ | 50% | 37% | 5% | 0.6% | 2% |
| B++MSC | 70% | 18% | 3% | 0.1% | 15% |
| B++MSC-IFNγ | 45% | 28% | 15% | 0.3% | 5% |
.
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). https://atcmeetingabstracts.com/abstract/inflammatory-conditions-switch-the-effect-of-msc-on-b-cells-from-pro-tolerogenic-to-anti-proliferative/. Accessed November 22, 2024.« Back to 2016 American Transplant Congress