الفهرس 
chapter 1Only 14 pages are availabe for public view
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Abstract
Gangliosides (glycosphingolipids) reduce antibody production by inhibiting B cell receptors (BCR)-signalling. It has been shown that a co-presentation of gangliosides and polyethylene glycol (PEG) on the same liposomes suppresses anti-PEG IgM production in mice. In addition, it was observed that plasmid DNA (pDNA) incorporated in PEGylated cationic liposomes (PCLs) induces anti-DNA IgM, which could be a hurdle to the development of efficient gene delivery systems. Therefore, the focus of this study was to determine if the co-presentation of gangliosides and DNA on the same PCL would suppress antibody production against DNA. PCL including DNA-induced anti-PEG IgM production and anti-DNA IgM production. The extent of anti-PEG and anti-DNA production was likely dependent on the immunogenicity of the complexed DNA. Treatment of clodronate-containing liposomes, which causes a depletion of phagocytic cells, suppressed anti-PEG IgM production from PCL that did not include DNA, but failed to suppress anti-PEG IgM production from PCL that complexed DNA (PCLD). Both anti-PEG IgM and anti-DNA IgM was induced in T-cell deficient nude mice as well as in normal mice following treatment with PCL and PCLD, respectively. These results indicate that phagocytic cells contribute to anti-PEG IgM production, but not to anti-DNA IgM production, while T cells do not contribute to either form of antibody production. But phagocytic cells were greatly contributing to both B cell responses and tolerance mechanisms. from the point of antibody production, spleen is the main contributing lymphoid organ with the aid of peritoneal cavity and circulating B cells. PEG-specific B cells and DNA-specific B cells is the main players in the immune responses to PCLD. Depletion of marginal zone B cells (MZB cells) using cyclophosphamide effectively reduced both anti-PEG and anti-DNA IgM antibodies. Unfortunately, the co-presentation of gangliosides and DNA significantly reduced anti-PEG IgM production but did not reduce anti-DNA IgM production from treatment with PCLD. It appears that the immunosuppressive effect of gangliosides via the CD22 signaling pathway is limited only to anti-PEG immunity.