Exp Mol Med.  2003 Oct;35(5):385-392.

B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis

• Choi Y
• Kim JJ

Abstract

Host immune response has been considered as an important disease-modifying factor of periodontitis, however, which immune cell(s) or factor(s) are involved in the destruction of periodontium remains unclear. Previously, we reported that osteoclastogenesis is enhanced by activated B cells but suppressed by activated CD8(+)T cells. We present new data that B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis. Purified murine B cells were activated with anti-IgD mAb, IL-4, and anti-CD40 mAb, in the absence (B(Th2)) or presence of Th1 cytokines, either IL-2 (B(IL-2)) or IFN-gamma (B(IFN-gamma)). Each activated B cell population was co-cultured with RAW264.7 cells in the presence of soluble receptor activator of NF-kappaB ligand (sRANKL), and the effect on osteoclastic differentiation was evaluated. While B(Th2)increased osteoclastogenesis, B(IL-2)and B(IFN-gamma)suppressed it profoundly. To verify the mediating molecule(s), we analyzed cytokine profiles of the activated B cells. Compared to B(Th2), B(IL-2)expressed increased amount of IFN-gamma and B(IFN-gamma)expressed decreased amounts of IL-4, IL-5, and IL-10. IFN-gamma was a key negative regulator of osteoclastic differentiation, and mediated the inhibition by B(IL-2). These results suggest that Th1 cytokines may have new important roles in resistance to periodontitis, acting directly on osteoclasts or indirectly through B cells.

MeSH Terms

Animals
B-Lymphocytes/cytology/*drug effects/immunology
Base Sequence
Cell Differentiation/*drug effects
Cytokines/*pharmacology
Female
Giant Cells/cytology/drug effects
Interferon Type II/immunology/metabolism
Lymphocyte Activation/*drug effects
Mice
Molecular Sequence Data
Osteoclasts/*cytology/*drug effects
Phenotype
Support, Non-U.S. Gov't
Th1 Cells/*immunology
Tumor Necrosis Factor/pharmacology