Universität zu Köln

Moran Tovar, Roberto ORCID: 0000-0002-6291-9376 (2025). Molecular Binding and Antigen Dynamics at the Onset of the Immune Response. PhD thesis, Universität zu Köln.

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Abstract

B cells are a key component of adaptive immunity in vertebrates. They recognize pathogens and trigger an immune response, which involves antibody secretion and the formation of immunological memory. In the context of immune receptor repertoires, new experimental techniques have provided us with unprecedented high-throughput genomic and phenotypic data. For instance, it has been observed that upon immunization, the immune system produces potent, specific and fast recognition of antigens, while maintaining a spectrum of genetically distinct activated B cell lineages. Moreover, heavy-tailed clone size distributions have been observed in different populations of B cells. To explain some of these observations, I have developed a spatiotemporal model of molecular recognition of antigens by B cells. Applied to various immunization processes, such as infections or vaccination, the model studies the collective response of B cells, driven by proliferation and diffusion of the antigen. The fundamental molecular interaction between antigens and B cells is mediated by a general kinetic proofreading scheme. Furthermore, drawing inspiration from the density of states in statistical physics, I characterize the diversity of the B cell population in terms of its functionally- determined density of receptors. This approach allows us to study how the immune system encodes in large but limited receptor repertoires the capacity to recognize virtually any pathogen that threatens the host. The molecular recognition process, driven by exponential growth of the antigen, can be mapped onto a generalized Luria-Delbrück process, akin to the seminal fluctuation experiment in microbial evolution. Overall, this model predicts key biological and medical phenomena such as the existence of primary elite neutralizers and the age-related decline in de novo responses. Finally, application of the model to memory B cell responses can be used to construct mechanistic in vivo protective functions that have only been heuristically determined.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Moran Tovar, Roberto rmorantovar@gmail.com orcid.org/0000-0002-6291-9376 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-787067
Date:	31 July 2025
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Physics > Institut für Biologische Physik
Subjects:	Physics
Uncontrolled Keywords:	Keywords Language Immune system English Statistical physics English B cells English Stochastic processes English
Date of oral exam:	18 June 2025
Referee:	Name Academic Title Lässig, Michael Prof. Dr. Krug, Joachim Prof. Dr. Tiffeau-Mayer, Andreas Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/78706