Author's School

Graduate School of Arts & Sciences

Author's Department/Program

Biology and Biomedical Sciences: Immunology

Language

English (en)

Date of Award

Summer 9-1-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Chair and Committee

Thaddeus S. Stappenbeck

Abstract

IgA is the most abundant immunoglobulin produced in the body, most of which can be found at mucosal sites such as the intestine where it plays an important role at a critical intersection between the host immune system and the microbiota. In the work detailed here, I sought to investigate IgA delivery and stability using in vitro and in vivo methods. First, I developed a primary intestinal epithelial monolayer system, and utilized this system to evaluate factors that modulate IgA transcytosis. In vivo, I interrogated baseline levels of fecal IgA in WT mice and surprisingly observed a binary phenotype in fecal IgA levels between cages. I found that the dichotomous IgA levels were heritable, transmissible, and microbially driven. In addition, the IgA-Low phenotype was dominant and functionally resulted in increased intestinal injury by DSS. Utilizing the primary epithelial monolayer system and IgA transcytosis assay, I found that anaerobically cultured microbes from IgA-Low mice had proteolytic activity capable of degrading secretory component (SC) in vitro. These findings support the idea that degradation of SC in vivo would make IgA more susceptible to degradation itself. These studies highlight the ability of the microbiota to produce phenotypic effects through IgA modulation.

Comments

This work is not available online per the author’s request. For access information, please contact digital@wumail.wustl.edu or visit http://digital.wustl.edu/publish/etd-search.html.

Permanent URL: http://dx.doi.org/10.7936/K7V9863Z

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