Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner

Chamberlain, Gabriel; Lopez, Guillaume; Bourguignon, Léa; Laulhe, Xavier; Adda-Bouchard, Yasmine; Charpentier, Tania; Honce, r; Botten, j et Lamarre, Alain ORCID: https://orcid.org/0000-0002-7913-871X (2025). Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner PLOS Pathogens , vol. 21 , nº 7. pp. 1-22. DOI: 10.1371/journal.ppat.1013345.

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Résumé

The polyclonal, T-dependent nature of hypergammaglobulinemia during murine infection with LCMV is well defined, however the mechanism by which polyclonal B cells acquire antigens for presentation remains unknown. Here we use LCMV-specific CD4 + transgenic T cells to explore several hypotheses for B cell antigen uptake. We found that antigens produced by cells infected with LCMV in vitro are available to polyclonal B cells and their presentation to CD4+ T cells enabled robust co-activation. The in vitro nature of our model demonstrates that in vivo factors such as cytokine milieu and antigen release by NK/CD8+ are not required. We show that non-replicative UVC-irradiated LCMV enables antigen access to B cells, thus productive infection of B cells is not required for antigen acquisition. B cells loaded with LCMV antigens in vitro can efficiently present these antigens to CD4+ T cells in LCMV-infected mice, thereby validating our model in vivo. Using transmission electron microscopy we identified LCMV-GP bearing particles of various sizes including < 50nm, a size accessible to B cells via pinocytosis. The particles morphologically resemble exosomes or viral particles (infective or defective interfering). We show that polyclonal B cell access to Ag is maintained when exosome release or viral defective interfering particle release is inhibited. Finally, we used a monovalent Fab derived from the LCMV-neutralizing antibody KL25 to show that access to the viral GP1 protein is important in order for polyclonal B cells to efficiently acquire LCMV antigen for presentation, suggesting the presence of a GP1 receptor on B cells.

Type de document:	Article
Informations complémentaires:	document e1013345 This work was supported by operating grants from the Canadian Institutes of Health Research (CIHR) to AL (PJT-159525) and National Institutes of Health (NIH) to JWB (R01 AI171408 and R21 AI154198) and RH (T32HL076122). AL holds the Jeanne and J.-Louis Lévesque Research Chair in Immunovirology from the J.-Louis Lévesque Foundation
Mots-clés libres:	-
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	28 août 2025 19:47
Dernière modification:	28 août 2025 19:47
URI:	https://espace.inrs.ca/id/eprint/16583

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