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

Area of Science:

• Immunology
• Skeletal Biology
• Cell Biology

Background:

• The immune and skeletal systems are interconnected.
• B lymphocytes possess osteo-interactive properties.
• The receptor activator of NF-κB (RANK) ligand (RANKL)-RANK axis is crucial for lymphoid tissue and bone homeostasis.

Purpose of the Study:

• To investigate the role of the RANKL-RANK axis in B cell physiology.
• To characterize the B cell compartment in mice lacking RANKL (Rankl(-/-)).

Main Methods:

• Detailed characterization of the B cell compartment in Rankl(-/-) mice.
• Analysis of B cell populations, Ig serum levels, germinal center formation, and response to CD40 triggering.
• Assessment of regulatory B cells and IL-10 production.
• In vivo blockade of IL-10 receptor (IL-10-R).

Main Results:

• Rankl(-/-) mice exhibited a relative expansion of marginal zone B cells, B1 cells, and plasma cells.
• Increased serum Ig levels, spontaneous germinal center formation, and hyperresponse to CD40 triggering were observed.
• An increased frequency of regulatory B cells and augmented B cell-derived IL-10 production were noted.
• In vivo IL-10-R blockade reduced T cell-triggered plasma cell differentiation and restrained regulatory B cell expansion.

Conclusions:

• The RANKL-RANK axis plays a novel role in regulating B cell homeostasis.
• An unexpected link exists between IL-10, CD40 signaling, and the RANKL pathway in B cell regulation.