title: Transcriptome Analysis of B Cell Immune Functions in Periodontitis: Mucosal Tissue Responses to the Oral Microbiome in Aging.
abstract: Evidence has shown activation of T and B cells in gingival tissues in experimental models and in humans diagnosed with periodontitis. The results of this adaptive immune response are noted both locally and systemically with antigenic specificity for an array of oral bacteria, including periodontopathic species, e.g., Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. It has been recognized through epidemiological studies and clinical observations that the prevalence of periodontitis increases with age. This report describes our studies evaluating gingival tissue transcriptomes in humans and specifically exploiting the use of a non-human primate model of naturally occurring periodontitis to delineate gingival mucosal tissue gene expression profiles focusing on cells/genes critical for the development of humoral adaptive immune responses. Patterns of B cell and plasmacyte genes were altered in aging healthy gingival tissues. Substantial increases in a large number of genes reflecting antigen-dependent activation, B cell activation, B cell proliferation, and B cell differentiation/maturation were observed in periodontitis in adults and aged animals. Finally, evaluation of the relationship of these gene expression patterns with those of various tissue destructive molecules (MMP2, MMP9, CTSK, TNFα, and RANKL) showed a greater frequency of positive correlations in healthy tissues versus periodontitis tissues, with only MMP9 correlations similar between the two tissue types. These results are consistent with B cell response activities in healthy tissues potentially contributing to muting the effects of the tissue destructive biomolecules, whereas with periodontitis this relationship is adversely affected and enabling a progression of tissue destructive events.
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA; Division of Periodontics, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ebersole
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky , Lexington, KY , USA.
authors.forename: Sreenatha S
authors.initials: SS
authors.lastname: Kirakodu
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky , Lexington, KY , USA.
authors.forename: M John
authors.initials: MJ
authors.lastname: Novak
authors.affiliation: Caribbean Primate Research Center , Sabana Seca, PR , USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Orraca
authors.affiliation: Caribbean Primate Research Center, Sabana Seca, PR, USA; Division of Oral and Maxillofacial Surgery, College of Dentistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Janis Gonzalez
authors.initials: JG
authors.lastname: Martinez
authors.affiliation: Division of Oral and Maxillofacial Surgery, College of Dentistry, University of Kentucky , Lexington, KY , USA.
authors.forename: Larry L
authors.initials: LL
authors.lastname: Cunningham
authors.affiliation: Division of Periodontics, College of Dentistry, University of Kentucky , Lexington, KY , USA.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Thomas
authors.affiliation: Department of Statistics, College of Arts and Sciences, University of Kentucky , Lexington, KY , USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Stromberg
authors.affiliation: Division of Orthodontics, College of Dentistry, University of Kentucky , Lexington, KY , USA.
authors.forename: Subramanya N
authors.initials: SN
authors.lastname: Pandruvada
authors.affiliation: Center for Oral Health Research, College of Dentistry, University of Kentucky , Lexington, KY , USA.
authors.forename: Octavio A
authors.initials: OA
authors.lastname: Gonzalez
keywords: B cells; aging; gingival tissues; non-human primates; periodontitis