4.7 Article

Mast cells enhance proliferation of B lymphocytes and drive their differentiation toward IgA-secreting plasma cells

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BLOOD
卷 115, 期 14, 页码 2810-2817

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AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-10-250126

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  1. Italian Ministry of Health
  2. AIRC (Associazione Italiana Ricerca sul Cancro)
  3. Ministero dell'Istruzione
  4. Universita e Ricerca
  5. Agenzia Spaziale Italiana
  6. LR.11 del Friuli Venezia Giulia

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The evidence of a tight spatial interaction between mast cells (MCs) and B lymphocytes in secondary lymphoid organs, along with the data regarding the abundance of MCs in several B-cell lymphoproliferative disorders prompted us to investigate whether MCs could affect the proliferation and differentiation of B cells. To this aim, we performed coculture assays using mouse splenic B cells and bone marrow-derived MCs. Both nonsensitized and activated MCs proved able to induce a significant inhibition of cell death and an increase in proliferation of naive B cells. Such proliferation was further enhanced in activated B cells. This effect relied on cell-cell contact and MC-derived interleukin-6 (IL-6). Activated MCs could regulate CD40 surface expression on unstimulated B cells and the interaction between CD40 with CD40 ligand (CD40L) on MCs, together with MC-derived cytokines, was involved in the differentiation of B cells into CD138(+) plasma cells and in selective immunoglobulin A (IgA) secretion. These data were corroborated by in vivo evidence of infiltrating MCs in close contact with IgA-expressing plasma cells within inflamed tissues. In conclusion, we reported here a novel role for MCs in sustaining B-cell expansion and driving the development of IgA-oriented humoral immune responses. (Blood. 2010; 115(14): 2810-2817)

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