Studies on the mechanism of peptidoglycan- and lipopolysaccharide-induced polyclonal activation.
Peptidoglycan (PG) and lipopolysaccharide (LPS) are T cell-independent B cell mitogens and polyclonal activators in mice. The mechanism of in vitro proliferation and polyclonal activation of mouse splenocytes induced by PG from Staphylococcus aureus and LPS from Escherichia coli was further studied by using [3H]thymidine incorporation and protein A hemolytic plaque assays. Concanavalin A-generated suppressor cells suppressed both polyclonal and proliferative responses induced by PG, LPS, and pokeweed mitogen. The suppression of the proliferative responses was similar for all these mitogens, but was significantly less pronounced than the suppression of the polyclonal antibody response. Polyclonal activation induced by LPS was the most susceptible to suppression by concanavalin A-generated suppressor cells, and the suppression was significantly greater than in the PG-induced polyclonal response. Also, PG-induced polyclonal activation was not susceptible to inhibition by polymyxin B, which is an inhibitor of other B cell mitogens and polyclonal activators. For optimal generation of immunoglobulin-secreting cells, PG of LPS had to be present for at least 48 h after the initiation of the cultures. Removal of the mitogens after 4 or 24 h of incubation resulted in a suboptimal response. For effective induction of the proliferative response, the mitogens had to be present in cultures for over 24 h. Polyclonal-activating properties of staphylococcal cell wall components were also compared. PG was by far the most potent inducer of polyclonal antibodies. Teichoic acid was not active as a polyclonal activator, whereas purified cell wall and protein A were very weak inducers of polyclonal antibodies. These studies demonstrate that PG, in addition to LPS, can be a useful probe for studies on polyclonal activation.
D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010457:Peptidoglycan / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D013205:Staphylococcal Protein A / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D013682:Teichoic Acids / Q000494:pharmacology
D008070:Lipopolysaccharides; D010457:Peptidoglycan; D013205:Staphylococcal Protein A; D013682:Teichoic Acids; D003208:Concanavalin A; D011112:Polymyxin B