Inflammatory Conditions Dictate the Effect of Mesenchymal Stem or Stromal Cells on B Cell Function

Bibliographic Details
Title: Inflammatory Conditions Dictate the Effect of Mesenchymal Stem or Stromal Cells on B Cell Function
Authors: Franka Luk, Laura Carreras-Planella, Sander S. Korevaar, Samantha F. H. de Witte, Francesc E. Borràs, Michiel G. H. Betjes, Carla C. Baan, Martin J. Hoogduijn, Marcella Franquesa
Source: Frontiers in Immunology, Vol 8 (2017)
Publisher Information: Frontiers Media S.A., 2017.
Publication Year: 2017
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: B cell, immunomodulation, mesenchymal stem cell, plasmablast, regulatory B cell, indoleamine 2,3-dioxygenase, Immunologic diseases. Allergy, RC581-607
More Details: The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC–IFN-γ) to simulate inflammatory conditions. Mature B cells were obtained from spleens by CD43− selection. B cells were co-cultured with MSC and stimulated with anti-IgM, anti-CD40, and IL-2; and after 7 days, B cell proliferation, phenotype, Immunoglobulin-G (IgG), and IL-10 production were analyzed. MSC did not inhibit B cell proliferation but increased the percentage of CD38high CD24high B cells (Bregs) and IL-10 production, while MSC–IFN-γ significantly reduced B cell proliferation and inhibited IgG production by B cells in a more potent fashion but did not induce Bregs or IL-10 production. Both MSC and MSC–IFN-γ required proximity to target cells and being metabolically active to exert their effects. Indoleamine 2,3 dioxygenase expression was highly induced in MSC–IFN-γ and was responsible of the anti-proliferative and Breg reduction since addition of tryptophan (TRP) restored MSC properties. Immunological conditions dictate the effect of MSC on B cell function. Under immunological quiescent conditions, MSC stimulate Breg induction; whereas, under inflammatory conditions, MSC inhibit B cell proliferation and maturation through depletion of TRP. This knowledge is useful for customizing MSC therapy for specific purposes by appropriate pretreatment of MSC.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: http://journal.frontiersin.org/article/10.3389/fimmu.2017.01042/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2017.01042
Access URL: https://doaj.org/article/7d606eba61fa434b93c68d4278121de9
Accession Number: edsdoj.7d606eba61fa434b93c68d4278121de9
Database: Directory of Open Access Journals
More Details
ISSN:16643224
DOI:10.3389/fimmu.2017.01042
Published in:Frontiers in Immunology
Language:English