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 Unpublished reflections on beneficial autoantibodies and future directions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
- Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or 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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