Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells.
Mesenchymal or stromal stem cells (MSC) interact with cells of the immune system in multiple ways. Modulation of the immune system by MSC is believed to be a therapeutic option for autoimmune disease and transplant rejection. In recent years, B cells have moved into the focus of the attention as targets for the treatment of immune disorders. Current B-cell targeting treatment is based on the indiscriminate depletion of B cells. The aim of this study was to examine whether human adipose tissue-derived MSC (ASC) interact with B cells to affect their proliferation, differentiation, and immune function. ASC supported the survival of quiescent B cells predominantly via contact-dependent mechanisms. Coculture of B cells with activated T helper cells led to proliferation and differentiation of B cells into CD19(+) CD27(high) CD38(high) antibody-producing plasmablasts. ASC inhibited the proliferation of B cells and this effect was dependent on the presence of T cells. In contrast, ASC directly targeted B-cell differentiation, independently of T cells. In the presence of ASC, plasmablast formation was reduced and IL-10-producing CD19(+) CD24(high) CD38(high) B cells, known as regulatory B cells, were induced. These results demonstrate that ASC affect B cell biology in vitro, suggesting that they can be a tool for the modulation of the B-cell response in immune disease.
Nephrology and Transplantation, Department of Internal Medicine, University Medical Center, Rotterdam, The Netherlands.
M
M
Franquesa
F K
FK
Mensah
R
R
Huizinga
T
T
Strini
L
L
Boon
E
E
Lombardo
O
O
DelaRosa
J D
JD
Laman
J M
JM
Grinyó
W
W
Weimar
M G H
MG
Betjes
C C
CC
Baan
M J
MJ
Hoogduijn
D000273:Adipose Tissue / Q000166:cytology* / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D048708:Cell Growth Processes / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D018920:Coculture Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology
B cell; Immunomodulation; Mesenchymal stem cell; Plasmablast; Regulatory B cell (Breg)