PMID- 37205983
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20240425
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Print)
IS  - 2162-4011 (Linking)
VI  - 12
IP  - 1
DP  - 2023
TI  - B cells require licensing by dendritic cells to serve as primary 
      antigen-presenting cells for plasmid DNA.
PG  - 2212550
LID - 10.1080/2162402X.2023.2212550 [doi]
LID - 2212550
AB  - 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.
CI  - (c) 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.
FAU - Rastogi, Ichwaku
AU  - Rastogi I
AD  - Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, 
      WI, USA.
FAU - McNeel, Douglas G
AU  - McNeel DG
AUID- ORCID: 0000-0003-1471-6723
AD  - Carbone Comprehensive Cancer Center, University of Wisconsin-Madison, Madison, 
      WI, USA.
LA  - eng
GR  - P30 CA014520/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230515
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
RN  - 0 (Vaccines, DNA)
RN  - 9007-49-2 (DNA)
RN  - 0 (Adjuvants, Immunologic)
SB  - IM
MH  - Humans
MH  - *Dendritic Cells
MH  - *Vaccines, DNA/genetics/metabolism
MH  - Antigen Presentation/genetics
MH  - DNA/metabolism
MH  - Plasmids/genetics
MH  - Adjuvants, Immunologic/metabolism
PMC - PMC10190194
OTO - NOTNLM
OT  - Antigen presentation
OT  - B cell
OT  - DNA vaccine
OT  - dendritic cell
OT  - plasmid DNA
COIS- Douglas G. McNeel has ownership interest, has received research support, and 
      serves as consultant to Madison Vaccines, Inc. which has licensed intellectual 
      property related to this content. IR has no relevant potential conflicts of 
      interest.
EDAT- 2023/05/19 19:14
MHDA- 2023/05/22 06:42
PMCR- 2023/05/15
CRDT- 2023/05/19 15:35
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/19 19:14 [pubmed]
PHST- 2023/05/19 15:35 [entrez]
PHST- 2023/05/15 00:00 [pmc-release]
AID - 2212550 [pii]
AID - 10.1080/2162402X.2023.2212550 [doi]
PST - epublish
SO  - Oncoimmunology. 2023 May 15;12(1):2212550. doi: 10.1080/2162402X.2023.2212550. 
      eCollection 2023.