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

Dissertation

Date of Award

2009

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

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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