B cells activated in the presence of Th1 cytokines inhibit osteoclastogenesis.
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 (BTh2) or presence of Th1 cytokines, either IL-2 (BIL-2) or IFN-gamma (BIFN-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 BTh2 increased osteoclastogenesis, BIL-2 and BIFN-gamma suppressed it profoundly. To verify the mediating molecule(s), we analyzed cytokine profiles of the activated B cells. Compared to BTh2, BIL-2 expressed increased amount of IFN-gamma and BIFN-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 BIL-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.
Choi
Youngnim
Y
Department of Orofacial Infection and Immunity, College of Dentistry, Seoul National University, 28 Yungun-dong, Jongro-gu, Seoul 110-749, Korea. youngnim@snu.ac.kr
Kim
Jeong Jae
JJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects*; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma