Bacterial-responsive B lymphocytes induce periodontal bone resorption.
Host immune responses play a key role in periodontal diseases. We have found that B lymphocytes in human periodontal lesions bear abundant receptor activator of NF-kappaB ligand (RANKL), a major factor in the regulation of osteoclast differentiation. The purpose of this study was to evaluate Actinobacillus actinomycetemcomitans-responsive B lymphocytes in their level of RANKL expression and their effects on periodontal bone resorption. Congenitally athymic Rowett rats received injections of formalin-fixed A. actinomycetemcomitans into the gingival papillae, and donor B cells from normal rats immunized with A. actinomycetemcomitans were transferred via tail vein injection. We demonstrated that B cells from A. actinomycetemcomitans-immunized animals had greater levels of RANKL expression and induced a significantly higher level of osteoclast differentiation from RAW 264.7 cells than did nonimmune B cells that were not Ag specific. This activity was eliminated by incubation with the RANKL decoy receptor osteoprotegerin fusion protein. A. actinomycetemcomitans-binding B cell (ABB) and RANKL-expressing B cells were recovered from the gingival tissues of recipient rats transferred with ABB, but not from recipients of PBS nonimmune B cells or A. actinomycetemcomitans nonbinding B cells. Also, recipients of ABB exhibited increased osteoclast formation on the alveolar bone surface and significant periodontal bone resorption. This effect was antagonized by injection of osteoprotegerin fusion protein into the local gingival tissues. In summary, this study suggests that B lymphocytes can contribute to increased periodontal bone resorption in the absence of T lymphocytes. This effect is associated with the up-regulation of RANKL expression.
Han
Xiaozhe
X
Department of Immunology, The Forsyth Institute, Boston, MA 02115, USA.
Kawai
Toshihisa
T
Eastcott
Jean W
JW
Taubman
Martin A
MA
D000189:Actinobacillus Infections / Q000276:immunology*; D019264:Adoptive Transfer; D016976:Aggregatibacter actinomycetemcomitans; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000187:drug effects; D002454:Cell Differentiation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006023:Glycoproteins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000187:drug effects; D010010:Osteoclasts / Q000166:cytology / Q000276:immunology; D053244:Osteoprotegerin; D053245:RANK Ligand; D051381:Rats; D011923:Rats, Nude; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C506032:Tnfrsf11b protein, rat