This project has three parts involving the capacity of three different components of gram negative bacteria to stimulate mitogenesis of murine B cells. The first involves the question of whether the Haemophilus influenzae type b capsular polysaccharide is a murine B cell mitogen as reported in 1986. We found that vaccine quality polysaccharide is not, itself, a B cell mitogen and only research grade polysaccharide containing significant contamination with lipopolysaccharide was mitogenic. We hypothesized that the reported mitogen was likely to have been a contaminant present in that batch of vaccine. The second part of this project was to determine if an H. influenzae type b polysaccharide- meningococcal outer membrane protein conjugate vaccine (Hib-OMP) was a murine B cell mitogen like the outer membrane protein alone which was reported by two labs to be mitogenic. We found that Hib-OMP was indeed a mitogen for murine B cells. We speculate that this property might explain the enhanced immunogenicity of Hib-OMP compared to H. influenzae type b polyooligosaccharide-protein conjugate in young human infants. Under culture conditions where pokweed mitogen stimulates human B cells to divide, we were not able to demonstrate a mitogenic effect of Hib- OMP. Whether Hib-0MP would be a mitogen under other conditions is unknown. Thus, an antigen which is classified as a TI type 1 antigen, based on its behavior with murine B cells, may have enhanced immunogenicity in man even if it is not a B cell mitogen for human B cells. Finally, studies are in progress to determine if lipooligosaccharides from human pathogens such as H. influenzae, Neisseria meningitidis and Bordetella pertussis are more potent B cell mitogens than lipopolysaccharides. Our preliminary results indicate that there is no correlation between mitogenic capacity and 0-side chain length.
