B cells targeting parasites capture spatially linked antigens to secure T cell help
- Author(s)
- Gao, X; McNamara, HA; Lee, J; Lo, AF; Chatterjee, D; Spensberger, D; Fernandez-Ruiz, D; Walz, K; Wang, K; Kelly, HG; Pohl, K; Carreira, PE; Do, A; Xiong, L; Beattie, L; Spencer, AJ; Gray, DHD; Frischknecht, F; Rug, M; Cockburn, IA;
- Details
- Publication Year 2025-11-07,Volume 10,Issue #113,Page eadw0415
- Journal Title
- Science Immunology
- Abstract
- T cell-dependent antibody responses have been well studied in the context of small proteins and viruses. However, how B cells acquire and process antigens from large pathogens such as parasites remains poorly understood. Here, using Plasmodium sporozoites (SPZs) as a model, we investigated the formation of protective antibody responses against the circumsporozoite protein (CSP), a vaccine antigen expressed on the surfaces of SPZs. CSP-specific B cells took up CSP and bystander surface antigens during SPZ immunization and could obtain both intramolecular and intermolecular T cell help. Furthermore, prior exposure to blood-stage parasites-which predominantly share internal but not surface antigens with SPZs-can hinder the generation of anti-CSP antibodies. Thus, spatial relationships between the target antigens can affect CD4 T cell help to B cells. These data show how B cells obtain antigen for presentation to T cells and why malaria-exposed individuals have impaired antibody responses to CSP.
- Publisher
- AAAS
- Keywords
- Animals; *B-Lymphocytes/immunology; *Antigens, Protozoan/immunology; *Protozoan Proteins/immunology; Mice; Antibodies, Protozoan/immunology; Mice, Inbred C57BL; Sporozoites/immunology; *Malaria/immunology; *T-Lymphocytes, Helper-Inducer/immunology; Female
- Research Division(s)
- Immunology
- PubMed ID
- 41202148
- Publisher's Version
- https://doi.org/10.1126/sciimmunol.adw0415
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-11-11 11:22:12
Last Modified: 2025-11-11 11:22:24