Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients.
Human bone marrow multipotent mesenchymal stromal cells are progenitor cells that can be expanded in vitro and differentiate into various cells of mesodermal origin. They contribute to the bone marrow reticular niche, where mature B cells and long-lived plasma cells are maintained. Multipotent mesenchymal stromal cells were recently shown to modulate T- and B-cell proliferation and differentiation, dendritic cell maturation, and natural killer activity. These immunoregulatory properties encouraged a possible use of these cells to modulate autoimmune responses in humans. We studied the influence of bone marrow mesenchymal stem cells on highly purified B-cell subsets isolated from healthy donors and total B cells from pediatric systemic lupus erythematosus patients. Bone marrow mesenchymal stem cells promoted proliferation and differentiation into immunoglobulin-secreting cells of transitional and naive B cells stimulated with an agonist of Toll-like receptor 9, in the absence of B cell receptor triggering. They strongly enhanced proliferation and differentiation into plasma cells of memory B-cell populations. A similar effect was observed in response to polyclonal stimulation of B cells isolated from pediatric patients with systemic lupus erythematosus. This study casts important questions on bone marrow mesenchymal stem cells as a therapeutic tool in autoimmune diseases in which B-cell activation is crucially implicated in the pathogenesis of the disease.
Traggiai
Elisabetta
E
Second Division of Pediatrics, IRCCS, Institute G. Gaslini, Genova, Italy. elisabetta.traggiai@gmail.com
Volpi
Stefano
S
Schena
Francesca
F
Gattorno
Marco
M
Ferlito
Francesca
F
Moretta
Lorenzo
L
Martini
Alberto
A
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002648:Child; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology*; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000473:pathology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000819:agonists
D007136:Immunoglobulins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9