Inhibition of B-Cell Proliferation and Antibody Production by Mesenchymal Stromal Cells Is Mediated by T Cells

Abstract

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and antiinflammatory properties, represent a promising tool in immunoregulatory and regenerative cell therapy. Clarifying the interactions between MSCs and B-lymphocytes may be crucial for designing innovative MSC-based strategies in conditions in which B cells play a role, including systemic lupus erythematosus (SLE) and rejection of kidney transplantation. In this study, we show that, both in healthy subjects and in patients, in vitro B-cell proliferation, plasma-cell differentiation, and antibody production are inhibited by BM-derived MSCs when peripheral blood lymphocytes are stimulated with CpG, but not when sorted B cells are cultured with MSCs + CpG. Inhibition is restored in CpG + MSC cocultures when sorted T cells are added to sorted B cells, suggesting that this effect is mediated by T cells, with both CD4 + and CD8 + cells playing a role. Moreover, cell-cell contact between MSCs and T cells, but not between MSCs and B cells, is necessary to inhibit B-cell proliferation. Thus, the presence of functional T cells, as well as cell-cell contact between MSCs and T cells, are crucial for B-cell inhibition. This information can be relevant for implementing MSC-based therapeutic immune modulation in patients in whom T-cell function is impaired.

Mesenchymal Stromal Cells Protect Against Caspase 3-Mediated Apoptosis of CD19+Peripheral B Cells Through Contact-Dependent Upregulation of VEGF

“…inhibiting or supporting B cell proliferation and antibody production depending on the presence of T cells in the co-culture [21,22]. MSC inhibit the proliferation and differentiation of stimulated B cells in whole peripheral blood lymphocyte populations or in co-culture with CD4 + T cells, but support proliferation and antibody production when cultured with pure B cell populations [21,22].…”

“…MSC inhibit the proliferation and differentiation of stimulated B cells in whole peripheral blood lymphocyte populations or in co-culture with CD4 + T cells, but support proliferation and antibody production when cultured with pure B cell populations [21,22].…”

Mesenchymal Stem Cells: Innovative Therapeutic Intervention for Autoimmune Rheumatic Diseases

“…This effect is also mediated by T cells [19,20] (Figure1). On the other hand, in the innate immunity system, there is the participation of mature DC (mDC), which plays a primordial role in the presentation of naive T-cell antigens.…”

“…The principal immuno-regulatory effects of MSCs are exerted in adaptive immunity to T cells as follows: [14] b) Induce division arrest and energy of activated T cells, accumulating T cells in the G0/G1 cell-cycle phase [15] c) Inhibit T-cell proliferation [16] d) Diminish cytotoxicity mediated by CD8+ cytotoxic T cells [17] and e) Promote the production of T regs cells CD4+ and CD25+, potent immune-suppressor cells that aid in maintaining homeostasis and tolerance to their own antigens [18,19].…”

Adenosine production: a common path for mesenchymal stem-cell and regulatory T-cell-mediated immunosuppression

“…Furthermore, not only MSCs affect dendritic cell recruitment, maturation, and function but also significantly reduce monocyte differentiation into the dendritic cell type [149][150][151][152][153]. Last but not least, MSCs alter the phenotype, proliferation, cytotoxic potential, and cytokine secretion of NK-cells [147,154,155] and decrease proliferation, differentiation, chemotactic properties of B-cells [156][157][158][159], acting over virtually all of the most important aspects of an immune response.…”