Origin and Development of the B cell response during Immunoregulatory Helminth Infections

Projektbeschreibung

Wie B-Zellen bei Helmintheninfektionen reagieren

Ein Viertel der Weltbevölkerung ist mit parasitären Würmern (Helminthen) infiziert, die die Immunantwort auf Impfstoffe und Infektionen beeinträchtigen können. Wir wissen zwar, dass diese Würmer das Immunsystem schwächen können, aber es ist nicht sicher, wie sie die Bildung schützender Antikörper durch B-Zellen beeinflussen. Das Team des ERC-finanzierten Projekts B-SELECT verfolgt das Ziel, zu erforschen, wie spezifische B-Zellen gebildet werden und wie Helminthen deren Entwicklung beeinträchtigen. Anhand der Durchführung von Untersuchungen auf molekularer Ebene wird im Rahmen des Projekts ermittelt, wie B-Zellen im Verlauf von Helmintheninfektionen aktiviert und ausgewählt werden. Die Ergebnisse werden Aufschluss darüber geben, wie wir die von Helminthen verursachten Störungen umgehen können, und die Wissenschaft beim Erfinden wirksamerer Impfstoffe unterstützen.

Ziel

One-fourth of the global population is currently infected with helminths, which modulate host immunity against not only their own antigens but also non-cognate antigens, including vaccines. While antigen-specific antibodies and memory B cells are essential for protection against infectious diseases, how the B cell response quality is influenced by helminths remains largely unknown. With my core expertise in studying responses to parasites at the level of single B cells and monoclonal antibodies, I aim to delineate the onset and quality of B cell responses formed during immunoregulatory helminth infections, impacting the development of effective vaccines.
The B cell response quality relies on recruiting antigen-specific naïve cells and selecting high-affinity B cells to form antibody-secreting cells and memory B cells. However, how these well-established mechanisms are impaired during B cell immunity modulated by helminths remains unknown. Therefore, the goal of this ERC proposal is to elucidate the molecular principles governing the formation and selection of antigen-specific B cells during helminth-induced immunoregulation and to identify strategies to mitigate modulation.
To achieve this, I will investigate the origin and development of de novo helminth antigen-specific B cell responses in the unique controlled helminth infections in naïve individuals and vaccine-specific B cell responses in residents of helminth-endemic areas. Access to clinical samples, advanced human tonsil organoids and transgenic mouse models, combined with my state-of-the-art expertise in studying antigen-specific B cells, uniquely positions me to uncover paradigm-shifting molecular principles that guide B cell responses during helminth infections. Ultimately, I aim to provide the first proof of concept to mitigate modulatory effects and rescue B cell response quality, paving the way to address global health challenges by inducing protective vaccine response in helminth-infected individuals.