Date: Saturday, April 29, 2017
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall D1
The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising therapeutic tool for immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of memory and plasmablast formation and induction of regulatory B cells. It is however unknown how MSC interact with B cells under inflammatory conditions.
In the present study MSC were isolated from adipose tissue and pre-treated with 50 ng/ml IFN-γ for 72h (MSC-IFN-γ) to simulate inflammatory conditions. Mature B cells were obtained from spleens by CD43– selection. B cells were co-cultured with MSC at a 10:1 ratio and stimulated with anti-IgM, anti-CD40 and IL-2. B cell proliferation and phenotype were analyzed by flow cytometry, and IgG and IL-10 production quantified by ELISA.
MSC were not capable of inhibiting the proliferation of B cells, while MSC-IFN-y significantly reduced B cell proliferation and were more potent in inhibiting IgG production by B cells. In contrast, MSC increased the percentage of IL-10 producing regulatory B cells (CD19+CD24hiCD38hi), whereas MSC-IFNy lacked this capacity. Culturing B cells with MSC-IFN-y in a transwell system in order to investigate the mechanisms of action abolished the effect on B cell proliferation. Indoleamine 2,3 dioxygenase (IDO) expression was highly induced in MSC-IFN-y. By abolishing the effect of IDO by the addition of tryptophan (TRP), B cell proliferation and induction of regulatory B cells was restored.
Therefore, immunological conditions dictate the effect of MSC on B cell function: under immunological quiescent conditions MSC stimulate regulatory B cell induction, whereas under inflammatory conditions MSC inhibit B cell proliferation and IgG production through depletion of TRP. This knowledge is useful for designing of MSC therapy for specific purposes by appropriate pre-treatment of MSC.
CITATION INFORMATION: Luk F, Carreras-Planella L, Korevaar S, de Witte S, Borràs F, Betjes M, Baan C, Hoogduijn M, Franquesa M. Inflammatory Conditions Dictate the Effect of MSC on B Cell Function. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Luk F, Carreras-Planella L, Korevaar S, Witte Sde, Borràs F, Betjes M, Baan C, Hoogduijn M, Franquesa M. Inflammatory Conditions Dictate the Effect of MSC on B Cell Function. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/inflammatory-conditions-dictate-the-effect-of-msc-on-b-cell-function/. Accessed November 26, 2020.
« Back to 2017 American Transplant Congress