The opposing roles of B-cell responses: Tissue-specific antibody determinants of disease progression versus recovery Restricted; Files Only
Babcock, Benjamin (Spring 2025)
Abstract
B cells are essential mediators of human immunity, yet there remains much to learn on their functional roles in health and disease. This dissertation investigates the function of B cells across the contexts of development, viral defense and recovery using both laboratory experimental and computational approaches. Chapters 1 and 2 focus on B-cell function in the context of the SARS-CoV-2 pandemic, characterizing the full breadth of human systemic and mucosal antibody responses associated with recovery from COVID-19. The results of this work highlight a previously unrecognized role of mucosal autoantibodies in the airway, contributing to recovery in mild and moderate COVID-19.
Chapters 3 and 4 continue the theme of B-cell investigation to better reveal the developmental landscape of human B cells by addressing challenges in single-cell RNA dataset integration caused by batch effects. By identifying donor-specific biological signals captured in dropout-prone transcripts, a biologically informed supervised approach was developed to resolve cellular lineages with greater fidelity. We propose an application of these insights to the prenatal origins of childhood B-cell acute lymphoblastic leukemia, establishing links between early-life B-cell ontogeny and disease susceptibility.
Together, these findings advance our understanding of B-cell biology, revealing critical roles of antibody and autoantibody responses in infection and recovery and providing a framework to map B-cell development across the human lifespan.
Table of Contents
Aims and structure of the dissertation
Chapter 1: A global emergency calls for a focus on mucosal B cells
Chapter 1.1. The mucosal sites of infection are key to recovery from COVID-19
Chapter 1.2. Interferons in COVID-19
Chapter 1.3. Autoantibodies in COVID-19
Chapter 1.4. Isotype, location, and timing define the protective anti-viral response
References
Chapter 2: Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19
Chapter 2.1: Abstract
Chapter 2.2: Introduction
Chapter 2.3: Results
Chapter 2.4: Discussion
Chapter 2.5: Methods
Chapter 2.6. Unpublished reflections on beneficial autoantibodies and future directions
Acknowledgements
Figures and Legends
References
Chapter 3: Dropout-susceptible transcripts are a major source of donor-associated batch effects in scRNA-seq data
Chapter 3.1. Overcoming batch effects: challenges to cell-lineage mapping are exacerbated by a mistaken understanding of batch effects
Chapter 3.2: Abstract
Chapter 3.3: Introduction
Chapter 3.4: Results
Chapter 3.5: Discussion
Chapter 3.6. Unpublished reflections on connecting biologically informed dataset integration methods to the identification of B-cell developmental lineages
Figures and Legends
References
Chapter 4: The lineages and origins of normal and malignant human B cells can be revealed with an optimized single-cell approach
Chapter 4.1. The early life origins of human B cells
Chapter 4.2. Future directions: Connecting ontogeny to B-cell leukemias
References
About this Dissertation
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File download under embargo until 22 May 2027 | 2025-01-09 17:13:41 -0500 | File download under embargo until 22 May 2027 |
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