Date of Award

Spring 2025

Document Type

Open Access Thesis

Department

Biomedical Science

First Advisor

Jason Kubinak

Abstract

The absorption of dietary lipids in the gut is necessary to maintain the metabolic tone of tissues. Inflammation in the gut can cause defects in lipid absorption, which can result in tissue wasting, otherwise known as cachexia. Cachexia is commonly observed in patients with inflammatory bowel disease and cancer patients. The underlying cause of cachexia is unknown, and there are currently no effective therapeutic options available to treat it. Lymphatic drainage in the small intestine (SI) is specialized to promote the transport of dietary lipids into circulation. Lacteals are blunt-ended lymphatic vessels localized to the central axes of villi in the SI where this process begins. Previous work by our lab has shown that B cell deficiency is associated with lipid malabsorption. Based on this observation, the purpose of this study was to empirically test the hypothesis that B cells, and specifically their secretion of immunoglobulin (IgA), are both necessary and sufficient to promote lacteal growth and lipid absorption in the gut. To address these questions, we have utilized a novel adoptive B cell transfer model coupled with immunofluorescence and high dimensional flow cytometry. Results from these experiments support our hypothesis by showing that B cells promote lacteal development and, consequently, lipid absorption. Importantly, our experiments demonstrate that both of these outcomes are dependent upon the ability of B cells to secrete IgA. Finally, we provide data supporting that IgA synthesis by B cells in the gut promotes lipid absorption that increases the mass of skeletal muscle in mice. In conclusion, the results of our work demonstrate for the first time that humoral immunity, and IgA synthesis specifically, promotes lipid absorption in the gut and skeletal muscle mass.

Rights

© 2025, Kenny Johnson

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