Mesenchymal stem cells suppress B-cell terminal differentiation.
OBJECTIVE
Mesenchymal stem cells (MSCs) have been shown to possess immunomodulatory properties on a diverse array of immune cell lineages. However, their effect on B lymphocytes remains unclear. We investigated the effect of MSCs on B-cell modulation with a special emphasis on gene regulation mediated by MSC humoral factors.


METHODS
MSCs were isolated from C57BL/6 bone marrow and expanded in culture. Splenic B cells were purified using anti-CD43 antibody and immunomagnetic beads. B cells and MSCs were cocultured in separate compartments in a transwell system. For B-cell stimulation, lipopolysaccharide was used in vitro and T-dependent and T-independent antigens were used in vivo.


RESULTS
In MSC cocultures, lipopolysaccharide-stimulated B-cell proliferation was suppressed, CD138(+) cell percentage decreased, and the number of apoptotic CD138(+) cells decreased. In the B/MSC coculture, the IgM(+) cell percentage was higher and the IgM amount released in the medium was lower than in the control. The B-lymphocyte-induced maturation protein-1 messenger RNA expression in the coculture was suppressed throughout the 3-day culture period. Conditioned media derived from MSC cultures prevented terminal differentiation of B cells in vitro and significantly suppressed the antigen-specific immunoglobulin M and immunoglobulin G1 secretion in mice immunized with T-cell-independent as well as T-cell-dependent antigens in vivo.


CONCLUSIONS
Results indicate that humoral factor(s) released by MSCs exert a suppressive effect on the B-cell terminal differentiation. Suppression may be mediated through inhibition of B-lymphocyte-induced maturation protein-1 expression, but the nature of the factor(s) is yet to be determined.
Asari
Sadaki
S
Southern California Islet Cell Resources Center, Department of Diabetes, Endocrinology, and Metabolism, Beckman, Research Institute of the City of Hope, Duarte, Calif. 91010, USA.
Itakura
Shin
S
Ferreri
Kevin
K
Liu
Chih-Pin
CP
Kuroda
Yoshikazu
Y
Kandeel
Fouad
F
Mullen
Yoko
Y
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D000074462:Positive Regulatory Domain I-Binding Factor 1; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D053668:Syndecan-1 / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; C513258:Prdm1 protein, mouse; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1