The inability of infants and young children to mount adequate antibody responses to certain bacterial polysaccharide antigens including capsular polysaccharides of Strep. pneumoniae and H. Flu. type b has limited the effectiveness of vaccines in protecting this highly susceptible age group against infection with these organisms. The immunological basis for the infant's deficient antibody responses to bacterial polysaccharides has been unclear. In studies of mice, we have obtained evidence that NK cells physiologically down-regulate antibody responses to pneumococcal polysaccharides, and that this down-regulatory effect is the primary factor responsible for the inadequate response of infants to these antigens. This project is designed to confirm and extend these findings with the goal of elucidating how NK cells exert this inhibitory effect, why these antibody responses are more inhibited in infants than in adults, and whether the enhanced immunogenicity of protein-conjugates of bacterial polysaccharides is related to the ability to bypass NK cell down- regulation. The effect of NK cell depletion or supplementation on in vivo and in vitro anti-pneumococcal antibody responses of weanling and adult mice will be tested in terms of the temporal relationship to depletion or supplementation, the kinetics and Ig subclass distribution of antibody responses, and specificity. The in vitro anti-phophorylcholine response in various strains of mice will be used as a model system to investigate the mechanism of NK down-regulation. The role of NK cells in regulating the weak response of infants to H. Flu type b polysaccharide will be examined.