title: Mast cells control the expansion and differentiation of IL-10-competent B cells.
abstract: The discovery of B cell subsets with regulatory properties, dependent on IL-10 production, has expanded our view on the mechanisms that control inflammation. Regulatory B cells acquire the ability to produce IL-10 in a stepwise process: first, they become IL-10 competent, a poised state in which B cells are sensitive to trigger signals but do not actually express the Il-10 gene; then, when exposed to appropriate stimuli, they start producing IL-10. Even if the existence of IL-10-competent B cells is now well established, it is not yet known how different immune cell types cross talk with B cells and affect IL-10-competent B cell differentiation and expansion. Mast cells (MCs) contribute to the differentiation and influence the effector functions of various immune cells, including B lymphocytes. In this study, we explored whether MCs could play a role in the expansion of IL-10-competent B cells and addressed the in vivo relevance of MC deficiency on the generation of these cells. We show that MCs can expand IL-10-competent B cells, but they do not directly induce IL-10 production; moreover, the absence of MCs negatively affects IL-10-competent B cell differentiation. Noteworthy, our findings reveal that the CD40L/CD40 axis plays a significant role in MC-driven expansion of IL-10-competent B cells in vitro and highlight the importance of MC CD40L signaling in the colon.
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy;
authors.forename: Francesca
authors.initials: F
authors.lastname: Mion
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy;
authors.forename: Federica
authors.initials: F
authors.lastname: D'Incà
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy;
authors.forename: Luca
authors.initials: L
authors.lastname: Danelli
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy;
authors.forename: Barbara
authors.initials: B
authors.lastname: Toffoletto
authors.affiliation: Tumor Immunology Unit, Human Pathology Section, Department of Health Sciences, University of Palermo, 90127 Palermo, Italy;
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy;
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.affiliation: Unità di Immunologia Molecolare, Dipartimento di Oncologia Sperimentale e Medicina Molecolare, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, 20133 Milan, Italy;
authors.forename: Alessia
authors.initials: A
authors.lastname: Burocchi
authors.affiliation: Unità di Immunologia Molecolare, Dipartimento di Oncologia Sperimentale e Medicina Molecolare, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, 20133 Milan, Italy;
authors.forename: Alice
authors.initials: A
authors.lastname: Rigoni
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, 80336 Munich, Germany;
authors.forename: Norbert
authors.initials: N
authors.lastname: Gerdes
authors.affiliation: Institute for Cardiovascular Prevention, Ludwig-Maximilians University, 80336 Munich, Germany; Experimental Vascular Biology Laboratory, Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, 1105AZ Amsterdam, the Netherlands; and.
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
authors.affiliation: Tumor Immunology Unit, Human Pathology Section, Department of Health Sciences, University of Palermo, 90127 Palermo, Italy;
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Unità di Immunologia Molecolare, Dipartimento di Oncologia Sperimentale e Medicina Molecolare, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, 20133 Milan, Italy;
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
authors.affiliation: Laboratory of Molecular Immunogenetics, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy;
authors.forename: Gaetano
authors.initials: G
authors.lastname: Vitale
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, 33100 Udine, Italy; carlo.pucillo@uniud.it.
authors.forename: Carlo E
authors.initials: CE
authors.lastname: Pucillo
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D055354:Exosomes / Q000378:metabolism; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D019013:CD40 Antigens; D016753:Interleukin-10; D023201:CD40 Ligand