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J Leukoc Biol. 2014 Aug;96(2):349-57. doi: 10.1189/jlb.4A0214-095R. Epub 2014 Apr 29.

B cells promote obesity-associated periodontitis and oral pathogen-associated inflammation.

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Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA;
Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, Massachusetts, USA; and.
Department of Periodontology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts, USA.
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA;


Individuals with T2D and PD suffer significantly from the ability of one disease to intensify the other. Disease-associated inflammation is one mechanism thought to fuel this pathogenic feed-forward loop. Several lines of evidence indicate that proinflammatory B cells promote T2D and PD; thus, B cells are top candidates for a cell type that predisposes PD in T2D. To test directly the role of B cells in T2D-associated PD, we compared outcomes from oral Porphyromonas gingivalis challenge of lean WT or B cell-null mice with outcomes from mice that were obese and insulin-resistant before challenge. Obese WT mice responded to oral P. gingivalis challenge with significant periodontal bone loss, whereas obese B cell-null mice were protected completely from PD. By contrast, lean WT and B cell-null mice suffer similar periodontal bone loss in response to oral pathogen. B cells from obese/insulin-resistant hosts also support oral osteoclastogenesis and both oral and systemic production of inflammatory cytokines, including pro-osteoclastogenic TNF-α and MIP-2, an ortholog of human IL-8. B cells furthermore impact AT inflammation in obese, P. gingivalis-infected hosts. Taken together, these data show that fundamentally different mechanisms regulate PD in lean and obese hosts, with B cells able to promote PD only if the hosts are "primed" by obesity. These results justify more intense analysis of obesity-associated changes in B cells that predispose PD in human T2D.


B lymphocyte; Porphyromonas gingivalis; cytokine; mouse model; type 2 diabetes

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