Mast cells enhance proliferation of B lymphocytes and drive their differentiation toward IgA-secreting plasma cells.
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.
Merluzzi
Sonia
S
Department of Biomedical Science and Technology, University of Udine, Udine, Italy.
Frossi
Barbara
B
Gri
Giorgia
G
Parusso
Serena
S
Tripodo
Claudio
C
Pucillo
Carlo
C
D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D053668:Syndecan-1 / Q000096:biosynthesis / Q000276:immunology
D019013:CD40 Antigens; C508600:IL6 protein, human; D007070:Immunoglobulin A; D015850:Interleukin-6; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D023201:CD40 Ligand