Inflammatory conditions dictate the effect of MSC on B cell function

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F. Luk, L. Carreras-Planella, S.S. Korevaar, S.F.H. de Witte, F.E. Borràs, M.G.H. Betjes, C.C. Baan, M.J. Hoogduijn, M. Franquesa

Chair(s): Prof. dr. C.C. Baan & dr. M.R. Rookmaaker

Wednesday 8 march 2017

18:30 - 18:42h at Hendrik Marsmanzaal

Categories: Parallel - Basaal

Parallel session: Parallelsessie V – Basaal 1 - Analyse niet-hematopoietische cellen in orgaantransplantatie

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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⁺CD24^hiCD38^hi), 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.