Thesis defense Laura Lighaam

On 27 September 2024 Laura Lighaam defended her PhD thesis 'The features and dynamics of lgG4 B cell responses: lnsights in B cell-mediated immune tolerance' at the University of Amsterdam

Promotor
Prof SM van Ham PhD

Co-promotor
T Rispens PhD

Venue
Agnietenkapel, Unversity of Amsterdam

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Abstract

B cells are traditionally known for their role in producing antibodies, but are more and more recognized for their involvement in immune regulation. This thesis focuses on IgG4 B cells, a unique subset involved in immune tolerance, and characterizes their behavior in comparison to other B cell subclasses, such as IgG1. By identifying a specific antibody capable of detecting IgG4 on the cell surface, the research offers new insights into the function and characteristics of these cells.
The findings reveal that IgG4 B cells, although a small fraction of the overall B cell population, are as capable of producing antibodies as IgG1 B cells. However, the IgG4 response tends to be shorter-lived, requiring continuous replenishment from the memory B cell pool. This transient nature might be linked to the distinct chemokine receptor profile of IgG4 B cells, which is influenced by IL-4 during class switch recombination. This profile appears to limit their localization in secondary lymphoid organs, contributing to their shorter-lived responses.
Furthermore, the role of IL-10-producing B cells in immune regulation is explored, challenging the notion that these cells represent a stable regulatory subset. Instead, IL-10 production in B cells may be a transient phase, possibly linked to IgG4 class switching, hinting at a complex relationship between humoral and cellular immune tolerance.
This thesis calls for more integrated research, highlighting the importance of studying immune responses in a broader context using advanced methods like systems biology, transcriptomics, and proteomics to better understand B cell-mediated immunity.