The evidence that periodontitis-associated bacteria contain potent PBA factors is very strong. Clearly, antibodies directed against non-oral antigens are produced in the inflamed periodontal lesion, and PBA appears to contribute to that production. It is also clear that B cells and plasma cells are the major cell types in the periodontal lesion. Furthermore, alterations in the regulation of B-cell responses to PBA factors are associated with severe periodontal disease. However, evidence demonstrating that activated B cells and plasma cells are directly involved in the pathogenic mechanisms leading to destruction of the periodontal support is still circumstantial. Polyclonal B-cell activation and potential pathways by which PBA-stimulated cells could be involved in periodontal destruction remain largely hypothetical. It appears that IL-1 is an important osteoclast-activating agent, and that LPS, which is a potent PBA factor in many systems, can elicit IL-1 production by B cells as well as by the monocyte/macrophage lineage. Recent data indicating that IL-1 is produced by numerous malignant B-cell lines lend support for the idea that B-cell IL-1 could be important in bone resorption. It is also likely that polyclonal activation may lead to production of autoantibody such as anti-type I and anti-type III collagens, and the destruction of self tissues through ADCC reactions, immune complex formation, and complement activation. Further research is needed to determine how the B cell/plasma cell may participate in tissue injury in periodontitis, and how the B-cell response to PBA factors is regulated.