All ETDs from UAB

Advisory Committee Chair

John F Kearney

Advisory Committee Members

Peter D Burrows

Robinna G Lorenz

Charles O Elson

Harry Jr W Schroeder

Casey T Weaver

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Polysaccharides are important structural components of bacterial capsule and cell walls. Polysaccharide-specific antibodies are an important component of serologic memory capable of protecting against infection by pathogenic microorganisms. An understanding of the biology and function of polysaccharide specific B cells is necessary for formulation of vaccines designed to induce polysaccharide specific memory and long-lived antibody production. The goal of this dissertation was to examine the development of naïve DEX-specific B cells and examine their capacity to generate memory and long-lived plasma cells in response to polysaccharide α 1→3-dextran (DEX), which is expressed by the opportunistic pathogens Enterobacter cloacae, Histoplasma capsulatum and Aspergilillus fumigatus. In the first study we examined the development of DEX-specific B cells in naïve mice and the ability of DEX-expressing microorganisms to promote development of DEX-specific memory B cells. In naive mice DEX-specific B cells preferentially enriched in MZ and B1b B cell populations. Challenge with DEX or DEX-expressing microorganisms resulted in the activation of MZ B cells and rapid production of peak titers of DEX-specific antibodies followed by the formation of long-lived DEX-specific B1b B cells capable of sustaining DEX-specific antibody production for up to 150 days. DEX-specific B1b B cells provided enhanced production of DEX-specific antibodies after secondary challenge in a manner independent of germinal center and T cell help, but instead dependent upon their capacity to self-renew. In the second study we investigated the ability of DEX to induce the formation of long-lived plasma cells. We examined the biology of DEX-specific plasma cells induced in response to DEX demonstrating that DEX did not generate long-lived plasma cells, but instead the generation of short-lived plasmablast and plasma cells, which were dependent upon DEX persistence. This study demonstrated an essential role for polysaccharide persistence in the maintaining long-lived polysaccharide-specific antibody production. Collectively these findings demonstrated that polysaccharides are capable of generating long-lived memory B cells and that maintenance of DEX-specific antibody production was dependent upon persistence of DEX, which continually stimulated the generation of short-lived plasmablast and plasma cells.



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