LAUSR

The immunomodulatory capacity of mesenchymal stem stromal cells (MSC) makes them a promising therapeutic tool after s organ transplantation. The effects of MSC on B cells in vitro are cha terized by an abrogation of memory and plasmablast formation and duction of regulatory B cells. MSC infused in patients might encou an inflammatory environment which could influence the immunomod tory effect of MSC. Therefore, we investigated how MSC interact wi cells under inflammatory conditions. In the present study MSC were isolated from adipose tissue and treated with 50 ng/ml IFN-γ for 96h (MSC-IFN-γ) to simulate inflamma conditions. Mature B cellswere obtained from spleens byCD43selec B cells were co-cultured with MSC at a 10:1 ratio and stimulated with IgM, anti-CD40 and IL-2. B cell proliferation and phenotype were analy by flow cytometry, and IgG and IL-10 production quantified by ELISA. MSC were not capable of inhibiting the proliferation of B cells, w MSC-IFN-y significantly reduced B cell proliferation and were more po in inhibiting IgG production by B cells. In contrast, MSC increased the centage of IL-10 producing regulatory B cells (CD19+CD24hiCD3 whereas MSC-IFNy lacked this capacity. Culturing B cells with MSC-IF in a transwell system in order to investigate the mechanisms of ac abolished the effect on B cell proliferation. Indoleamine 2,3 dioxygen (IDO) expression was highly induced in MSC-IFN-y, leading to degrada and depletion of tryptophan (TRP). By abolishing the effect of IDOby the dition of TRP to the co-culture, B cell proliferation and induction of regula B cells was restored. Immunological conditions dictate the effect of MSC on B cell func under immunological quiescent conditions MSC stimulate regulato cell induction, whereas under inflammatory conditions MSC inhibit B proliferation and IgG production through depletion of TRP. This kn edge is useful for designing of MSC therapy for specific purposes by propriate pre-treatment of MSC. wer Health, Inc. All rights reserved.