Balancing defense and tolerance: B cell adaptation under chronic parasitic exposure

Abstract

Chronic and repeated exposure to pathogens, particularly helminth parasites, shapes the development and function of the human immune system. However, how persistent exposure influences B cell memory and immune regulation remains incompletely understood. This thesis investigates B cell adaptation under chronic parasitic exposure, aiming to define its effects on B cell memory responses and to identify helminth-derived molecules that promote regulatory B cell (Breg) development.

In the first part, bulk RNA sequencing of B cells from Schistosoma-infected and non-infected Gabonese children, before and after anthelminthic treatment, tried to identify transcriptional differences associated with infection. Mass cytometry profiling of B cells from Ghanaian, Indonesian, and Dutch individuals further revealed changes in B cell populations linked to continuous parasite exposure. The second part examines helminth-induced Breg cells and their therapeutic potential. Following a review of parasites, allergy, and regulatory immune cells, we showed that Schistosoma mansoni egg antigens, including IPSE/α1, induce IL-10-producing Breg in human and mouse cells, while additional egg-derived molecules retain this activity. Using chromatography, engineered glycans, and recombinant proteins, we identified schistosome molecules driving Breg development and established standardized approaches to induce and characterize Bregs in mice and humans.