IL-10 critically modulates B cell responsiveness in Rankl-/- mice

• Published in: The Journal of immunology (1950) 2015-05, Vol.194 (9), p.4144-4153
• Main Authors: Marrella, Veronica, Lo Iacono, Nadia, Fontana, Elena, Sobacchi, Cristina, Sic, Heiko, Schena, Francesca, Sereni, Lucia, Castiello, Maria Carmina, Poliani, Pietro Luigi, Vezzoni, Paolo, Cassani, Barbara, Traggiai, Elisabetta, Villa, Anna
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocytes - immunology; Interleukin-10 - immunology; Mice; Mice, Knockout; RANK Ligand - deficiency; RANK Ligand - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401977

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.