Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-07-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1013345 |
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| author | Gabriel Chamberlain Guillaume L Lopez Léa Bourguignon Xavier Laulhé Yasmine Adda-Bouchard Tania Charpentier Rebekah Honce Jason W Botten Alain Lamarre |
| author_facet | Gabriel Chamberlain Guillaume L Lopez Léa Bourguignon Xavier Laulhé Yasmine Adda-Bouchard Tania Charpentier Rebekah Honce Jason W Botten Alain Lamarre |
| author_sort | Gabriel Chamberlain |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1e5033d0a5fd4225ba3fb9dd239604bd |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1e5033d0a5fd4225ba3fb9dd239604bd2025-08-20T03:27:28ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-07-01217e101334510.1371/journal.ppat.1013345Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner.Gabriel ChamberlainGuillaume L LopezLéa BourguignonXavier LaulhéYasmine Adda-BouchardTania CharpentierRebekah HonceJason W BottenAlain LamarreThe 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.https://doi.org/10.1371/journal.ppat.1013345 |
| spellingShingle | Gabriel Chamberlain Guillaume L Lopez Léa Bourguignon Xavier Laulhé Yasmine Adda-Bouchard Tania Charpentier Rebekah Honce Jason W Botten Alain Lamarre Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner. PLoS Pathogens |
| title | Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner. |
| title_full | Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner. |
| title_fullStr | Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner. |
| title_full_unstemmed | Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner. |
| title_short | Polyclonal B cells acquire LCMV antigens in a GP1-dependent manner. |
| title_sort | polyclonal b cells acquire lcmv antigens in a gp1 dependent manner |
| url | https://doi.org/10.1371/journal.ppat.1013345 |
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