B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA
DNA vaccines have been an attractive approach for treating cancer patients, however have demonstrated modest immunogenicity in human clinical trials. Dendritic cells (DCs) are known to cross-present DNA-encoded antigens expressed in bystander cells. However, we have previously reported that B cells,...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2212550 |
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| author | Ichwaku Rastogi Douglas G. McNeel |
| author_facet | Ichwaku Rastogi Douglas G. McNeel |
| author_sort | Ichwaku Rastogi |
| collection | DOAJ |
| description | DNA vaccines have been an attractive approach for treating cancer patients, however have demonstrated modest immunogenicity in human clinical trials. Dendritic cells (DCs) are known to cross-present DNA-encoded antigens expressed in bystander cells. However, we have previously reported that B cells, and not DCs, serve as primary antigen-presenting cells (APCs) following passive uptake of plasmid DNA. Here we sought to understand the requirements for B cells to present DNA-encoded antigens, to ultimately increase the immunogenicity of plasmid DNA vaccines. Using ovalbumin-specific OT-1 CD8+ T cells and isolated APC populations, we demonstrated that following passive uptake of plasmid DNA, B cells but not DC, can translate the encoded antigen. However, CD8 T cells were only activated by B cells when they were co-cultured with DCs. We found that a cell-cell contact is required between B cells and DCs. Using MHCI KO and re-purification studies, we demonstrated that B cells were the primary APCs and DCs serve to license this function. We further identified that the gene expression profiles of B cells that have been licensed by DCs, compared to the B cells that have not, are vastly different and have signatures similar to B cells activated with a TLR7/8 agonist. Our data demonstrate that B cells transcribe and translate antigens encoded by plasmid DNA following passive uptake, however require licensing by live DC to present antigen to CD8 T cells. Further study of the role of B cells as APCs will be important to improve the immunological efficacy of DNA vaccines. |
| format | Article |
| id | doaj-art-af53b999f84b4843935a5e344743f9b2 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-af53b999f84b4843935a5e344743f9b22024-12-27T17:34:38ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2212550B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNAIchwaku Rastogi0Douglas G. McNeel1Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, USACarbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, WI, USADNA vaccines have been an attractive approach for treating cancer patients, however have demonstrated modest immunogenicity in human clinical trials. Dendritic cells (DCs) are known to cross-present DNA-encoded antigens expressed in bystander cells. However, we have previously reported that B cells, and not DCs, serve as primary antigen-presenting cells (APCs) following passive uptake of plasmid DNA. Here we sought to understand the requirements for B cells to present DNA-encoded antigens, to ultimately increase the immunogenicity of plasmid DNA vaccines. Using ovalbumin-specific OT-1 CD8+ T cells and isolated APC populations, we demonstrated that following passive uptake of plasmid DNA, B cells but not DC, can translate the encoded antigen. However, CD8 T cells were only activated by B cells when they were co-cultured with DCs. We found that a cell-cell contact is required between B cells and DCs. Using MHCI KO and re-purification studies, we demonstrated that B cells were the primary APCs and DCs serve to license this function. We further identified that the gene expression profiles of B cells that have been licensed by DCs, compared to the B cells that have not, are vastly different and have signatures similar to B cells activated with a TLR7/8 agonist. Our data demonstrate that B cells transcribe and translate antigens encoded by plasmid DNA following passive uptake, however require licensing by live DC to present antigen to CD8 T cells. Further study of the role of B cells as APCs will be important to improve the immunological efficacy of DNA vaccines.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2212550Antigen presentationB celldendritic cellDNA vaccineplasmid DNA |
| spellingShingle | Ichwaku Rastogi Douglas G. McNeel B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA OncoImmunology Antigen presentation B cell dendritic cell DNA vaccine plasmid DNA |
| title | B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA |
| title_full | B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA |
| title_fullStr | B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA |
| title_full_unstemmed | B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA |
| title_short | B cells require licensing by dendritic cells to serve as primary antigen-presenting cells for plasmid DNA |
| title_sort | b cells require licensing by dendritic cells to serve as primary antigen presenting cells for plasmid dna |
| topic | Antigen presentation B cell dendritic cell DNA vaccine plasmid DNA |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2212550 |
| work_keys_str_mv | AT ichwakurastogi bcellsrequirelicensingbydendriticcellstoserveasprimaryantigenpresentingcellsforplasmiddna AT douglasgmcneel bcellsrequirelicensingbydendriticcellstoserveasprimaryantigenpresentingcellsforplasmiddna |