ASI SponsorMerluzzi, SoniaSoniaMerluzziFrossi, BarbaraBarbaraFrossiGri, GiorgiaGiorgiaGri2020-09-172020-09-172010-04-01https://hdl.handle.net/20.500.13025/3380The 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.AnimalsAntigensCD40CD40 LigandCD40 Ligand: biosynthesisCD40 Ligand: immunologyCD40: biosynthesisCD40: immunologyCell CommunicationCell Communication: immunologyCell DeathCell Death: immunologyCell DifferentiationCell Differentiation: immunologyCell ProliferationGene Expression RegulationGene Expression Regulation: immunologyHumansHumoralImmunityImmunoglobulin AImmunoglobulin A: immunologyImmunoglobulin A: metabolismInterleukin-6Interleukin-6: biosynthesisInterleukin-6: immunologyLymphocyte ActivationLymphocyte Activation: immunologyMast CellsMast Cells: immunologyMicePlasma CellsPlasma Cells: immunologyPlasma Cells: secretionSyndecan-1Syndecan-1: biosynthesisSyndecan-1: immunologyArticle Journalhttp://bloodjournal.hematologylibrary.org/cgi/content/abstract/115/14/281054dcce0e8580fe1368eeb47e