ENHANCED POLYCLONAL B CELL ACTIVATION BY PMN LYSATES

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Periodontitis lesions are histologically characterized by a dense infiltration of neutrophils (PMNs), T cells, and an unusually large accumulation of activated B cells. There is increasing evidence that the large number of B cells in these lesions is the result of nonspecific, polyclonal B cell activation (PBA) induced by the subgingival plaque bacteria. The cell walls of Fusobacterium nucleatum (FN) and other gram negative bacteria frequently isolated from periodontitis lesions are very potent stimulants of human PBA in vitro. In the course of studying cellular regulation of FN-induced PBA (FN-PBA) we found that the addition of sonicated neutrophil (PMN) lysates to lymphocyte cultures increased PBA induced by FN cell walls two- to five-fold. Lysates of sonicated lymphocytes did not enhance FN-PBA. The purpose of this proposal is to isolate and identify the PMN factor(s) which enhance FN-PBA in vitro. Specifically, PMNs will be fractionated into 1) cytoplasm, 2) nuclear pellets, 3) granules (lysosomes), and 4) membrane fractions through routine procedures. Each fraction will then be tested for the capacity to enhance FN-PBA in human lymphocyte cultures. The data from these experiments will enable us to detail the mechanism of action of the PMN factor(s) on B cell activation. Polyclonal B cell activation is associated with several chronic inflammatory diseases in which 1) microbial-induced PBA is speculated to be involved in the disease, and 2) PMNs and activated B cells are seen in close juxtaposition. PMN factors may therefore be involved in the enhanced nonspecific activation of B cells observed in periodontitis as well as other chronic inflammatory diseases.