title: IL-10 critically modulates B cell responsiveness in Rankl-/- mice.
abstract: The immune and the skeletal system are tightly interconnected, and B lymphocytes are uniquely endowed with osteo-interactive properties. In this context, receptor activator of NF-κB (RANK) ligand (RANKL) plays a pivotal role in lymphoid tissue formation and bone homeostasis. Although murine models lacking RANK or RANKL show defects in B cell number, the role of the RANKL-RANK axis on B physiology is still a matter of debate. In this study, we have characterized in detail B cell compartment in Rankl(-/-) mice, finding a relative expansion of marginal zone B cells, B1 cells, and plasma cells associated with increased Ig serum levels, spontaneous germinal center formation, and hyperresponse to CD40 triggering. Such abnormalities were associated with an increased frequency of regulatory B cells and augmented B cell-derived IL-10 production. Remarkably, in vivo IL-10-R blockade reduced T cell-triggered plasma cell differentiation and restrained the expansion of regulatory B cells. These data point to a novel role of the RANKL-RANK axis in the regulation of B cell homeostasis and highlight an unexpected link between IL-10 CD40 signaling and the RANKL pathway.
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Unità Operativa di Milano, Consiglio Nazionale delle Richerche, 20138 Milan, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy;
authors.forename: Veronica
authors.initials: V
authors.lastname: Marrella
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Unità Operativa di Milano, Consiglio Nazionale delle Richerche, 20138 Milan, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy;
authors.forename: Nadia
authors.initials: N
authors.lastname: Lo Iacono
authors.affiliation: Department of Molecular and Translational Medicine, Pathology Unit, University of Brescia, 25121 Brescia, Italy;
authors.forename: Elena
authors.initials: E
authors.lastname: Fontana
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Unità Operativa di Milano, Consiglio Nazionale delle Richerche, 20138 Milan, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy;
authors.forename: Cristina
authors.initials: C
authors.lastname: Sobacchi
authors.affiliation: Novartis Institute for Research in Biomedicine, 4002 Basel, Switzerland;
authors.forename: Heiko
authors.initials: H
authors.lastname: Sic
authors.affiliation: Department of Pediatrics, University of Genova and Pediatrics II, Institute Giannina Gaslini, 16148 Genova, Italy; and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Schena
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sereni
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy.
authors.forename: Maria Carmina
authors.initials: MC
authors.lastname: Castiello
authors.affiliation: Department of Molecular and Translational Medicine, Pathology Unit, University of Brescia, 25121 Brescia, Italy;
authors.forename: Pietro Luigi
authors.initials: PL
authors.lastname: Poliani
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Unità Operativa di Milano, Consiglio Nazionale delle Richerche, 20138 Milan, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Vezzoni
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Unità Operativa di Milano, Consiglio Nazionale delle Richerche, 20138 Milan, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy;
authors.forename: Barbara
authors.initials: B
authors.lastname: Cassani
authors.affiliation: Novartis Institute for Research in Biomedicine, 4002 Basel, Switzerland;
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traggiai
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Unità Operativa di Milano, Consiglio Nazionale delle Richerche, 20138 Milan, Italy; Humanitas Clinical and Research Center, 20089 Rozzano, Italy; anna.villa@humanitasresearch.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Villa
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053245:RANK Ligand / Q000172:deficiency* / Q000276:immunology*
chemical_list: D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D016753:Interleukin-10