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 |