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

Descripción del proyecto

Estudio de la respuesta de los linfocitos B durante infecciones por helmintos

Una cuarta parte de la población mundial está infectada por gusanos parásitos (helmintos), que pueden afectar a las respuestas inmunitarias a las vacunas y las infecciones. Se sabe que los helmintos pueden debilitar el sistema inmunitario, pero se desconoce cómo afectan a la generación de anticuerpos protectores por parte de los linfocitos B. En el proyecto B-SELECT, financiado por el Consejo Europeo de Investigación, se pretende determinar cómo se forman los linfocitos B específicos y cómo los helmintos perjudican su desarrollo. El equipo del proyecto llevará a cabo estudios moleculares proyecto para estudiar la activación y selección de linfocitos B durante las infecciones por helmintos. Los resultados de la investigación podrían contribuir a esclarecer cómo sortear las interferencias causadas por los helmintos y ayudar a diseñar mejores vacunas.

Objetivo

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.