B cells targeting parasites capture spatially linked antigens to secure T cell help

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 <i>Plasmodium</i> 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.

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Publication Details

Journal
Science Immunology
Published
2025-11-07
DOI
https://doi.org/10.1126/sciimmunol.adw0415
Primary Topic
Malaria Research and Control
Type
article
Field-Weighted Citation Impact
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article

B cells targeting parasites capture spatially linked antigens to secure T cell help

Le Xiong, Melanie Rug, Hannah G. Kelly, Daniel Fernandez‐Ruiz et al.
Science Immunology
Malaria Research and Control
article

B cells targeting parasites capture spatially linked antigens to secure T cell help

Le Xiong, Melanie Rug, Hannah G. Kelly, Daniel Fernandez‐Ruiz, Kevin Walz, Adrian F. Lo, Hayley A. McNamara, Friedrich Frischknecht, Ian A. Cockburn, Dominik Spensberger, Patricia E. Carreira, Kai Pohl, Alexandra J. Spencer, Lynette Beattie, Daniel H.D. Gray, Deepyan Chatterjee, Xin Gao, Jiwon Lee, Ke Wang, Andrea Do
article en

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 <i>Plasmodium</i> 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.

Science ImmunologyVol. 10(113)
Australian National University (AU), The University of Melbourne (AU), Walter and Eliza Hall Institute of Medical Research (AU), Heidelberg University (DE), UNSW Sydney (AU), Humboldt-Universität zu Berlin (DE), Peter Doherty Institute (AU), University of Newcastle Australia (AU)
Openalex Percentile: Top 57%
Malaria Research and Control
DOISourceOpenAlex
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