Chronic inflammatory diseases, such as periodontal diseases, are characterized by a large accumulation of B cells an immunoglobulin-secreting plasma cells. The role of the B cells in these chronic lesions is poorly understood. Microorganisms isolated from dental plaque are known to possess soluble polyclonal B cell activators (PBAs) which may nonspecifically activate immunoglobulin synthesis in situ. Recent studies from our laboratory, employing a highly sensitive micro-enzyme linked immunosorbent assay (micro-ELISA), have shown the PBA components from Actinomyces viscosus can stimulate in vitro nonspecific release of immunoglobulins to unrelated bacterial antigens. Additional studies have suggested Fusobacterium nucleatum also possesses a potent PBA. The proposed studies will investigate the activation of human peripheral blood B cells from healthy individuals and periodontitis patients by soluble preparations of A. viscosus and F. nucleatum. The lymphocyte culture supernates will be assayed for total immunoglobulins (IgA, IgG, IgM), immunoglobulins specific for a battery of dental plaque bacterial antigens, and immunoglobulins specific for human tissue antigens (i.e. autoimmune antibodies). The in vitro immunoglobulin responses to the bacterial and human antigens will be compared to the titers to these antigens found in the donors' plasma. Since the A. viscosus-induced antibodies can react with several other antigens, the biological consequences of the antigen-antibody reaction will be studied with regard to opsonization (increased phagocytosis) of the bacteria, and complement fixation. Finally, the proposed study will investigate the cellular regulation of the A. viscosus- and F. nucleatum-induced polyclonal B cell response, measuring the effects of total and specific immunoglobulin synthesis. The data obtained from this study will advance our understanding of the immune mechanisms involved n periodontal disease as well as provide information which may be of prognostic or diagnostic value in periodontal disease.