Inhibition of B-cell proliferation and antibody production by mesenchymal stromal cells is mediated by T cells

Maria Manuela Rosado, Maria Ester Bernardo, Marco Scarsella, Antonella Conforti, Ezio Giorda, Simone Biagini, Simona Cascioli, Francesca Rossi, Isabella Guzzo, Marina Vivarelli, Luca Dello Strologo, Francesco Emma, Franco Locatelli, Rita Carsetti

Research output: Contribution to journalArticle

Abstract

Bone marrow (BM)-derived mesenchymal stromal cells (MSCs), endowed with immunosuppressive and anti-inflammatory 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.

Original languageEnglish
Pages (from-to)93-103
Number of pages11
JournalStem Cells and Development
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

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ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

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