Mast cells enhance proliferation of B lymphocytes and drive their differentiation toward IgA-secreting plasma cells
Merluzzi, Sonia ; Frossi, Barbara ; Gri, Giorgia ; et al. ; - ASI Sponsor
Apr - 2010
ISSN : 1528-0020 ;
journal : Blood

Issue : 14
type: Article Journal

Abstract
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.

keywords : Animals,Antigens,CD40,CD40 Ligand,CD40 Ligand: biosynthesis,CD40 Ligand: immunology,CD40: biosynthesis,CD40: immunology,Cell Communication,Cell Communication: immunology,Cell Death,Cell Death: immunology,Cell Differentiation,Cell Differentiation: immunology,Cell Proliferation,Gene Expression Regulation,Gene Expression Regulation: immunology,Humans,Humoral,Immunity,Immunoglobulin A,Immunoglobulin A: immunology,Immunoglobulin A: metabolism,Interleukin-6,Interleukin-6: biosynthesis,Interleukin-6: immunology,Lymphocyte Activation,Lymphocyte Activation: immunology,Mast Cells,Mast Cells: immunology,Mice,Plasma Cells,Plasma Cells: immunology,Plasma Cells: secretion,Syndecan-1,Syndecan-1: biosynthesis,Syndecan-1: immunology