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.
Southern California Islet Cell Resources Center, Department of Diabetes, Endocrinology, and Metabolism, Beckman, Research Institute of the City of Hope, Duarte, Calif. 91010, USA.
Sadaki
S
Asari
Shin
S
Itakura
Kevin
K
Ferreri
Chih-Pin
CP
Liu
Yoshikazu
Y
Kuroda
Fouad
F
Kandeel
Yoko
Y
Mullen
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