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.
| Original language | English |
|---|---|
| Pages (from-to) | 4144-4153 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 194 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - May 1 2015 |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
IL-10 critically modulates B cell responsiveness in rankl-/- mice. / 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.
In: Journal of Immunology, Vol. 194, No. 9, 01.05.2015, p. 4144-4153.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - IL-10 critically modulates B cell responsiveness in rankl-/- mice
AU - Marrella, Veronica
AU - Lo Iacono, Nadia
AU - Fontana, Elena
AU - Sobacchi, Cristina
AU - Sic, Heiko
AU - Schena, Francesca
AU - Sereni, Lucia
AU - Castiello, Maria Carmina
AU - Poliani, Pietro Luigi
AU - Vezzoni, Paolo
AU - Cassani, Barbara
AU - Traggiai, Elisabetta
AU - Villa, Anna
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84928501037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928501037&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1401977
DO - 10.4049/jimmunol.1401977
M3 - Article
C2 - 25825446
AN - SCOPUS:84928501037
VL - 194
SP - 4144
EP - 4153
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -