title: Inflammation enhances the vaccination potential of CD40-activated B cells in mice.
abstract: Vaccination with antigen-pulsed CD40-activated B (CD40-B) cells can efficiently lead to the in vivo differentiation of naive CD8+T cells into fully functional effectors. In contrast to bone marrow-derived dendritic cell (BMDC) vaccination, CD40-B cell priming does not allow for memory CD8+T-cell generation but the reason for this deficiency is unknown. Here, we show that compared to BMDCs, murine CD40-B cells induce lower expression of several genes regulated by T-cell receptor signaling, costimulation, and inflammation (signals 1-3) in mouse T cells. The reduced provision of signals 1 and 2 by CD40-B cells can be explained by a reduction in the quality and duration of the interactions with naive CD8+T cells as compared to BMDCs. Furthermore, CD40-B cells produce less inflammatory mediators, such as IL-12 and type I interferon, and increasing inflammation by coadministration of polyriboinosinic-polyribocytidylic acid with CD40-B-cell immunization allowed for the generation of long-lived and functional CD8+memory T cells. In conclusion, it is possible to manipulate CD40-B-cell vaccination to promote the formation of long-lived functional CD8+memory T cells, a key step before translating the use of CD40-B cells for therapeutic vaccination.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montréal, Québec, Canada.|Department of Microbiology, Infectious Diseases and Immunology, University of Montreal, Montréal, Québec, Canada.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Mathieu
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montréal, Québec, Canada.|Department of Microbiology, Infectious Diseases and Immunology, University of Montreal, Montréal, Québec, Canada.
authors.forename: Livia
authors.initials: L
authors.lastname: Odagiu
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montréal, Québec, Canada.
authors.forename: Léa
authors.initials: L
authors.lastname: Gaudot
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montréal, Québec, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Daudelin
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montréal, Québec, Canada.|Department of Medicine, University of Montreal, Montréal, Québec, Canada.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Melichar
authors.affiliation: Department of Medicine, University of Montreal, Montréal, Québec, Canada.|Research Centre, Centre Hospitalier de l'Université de Montréal (CRCHUM), University of Montreal and Institut du Cancer de Montréal, Montréal, Québec, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montréal, Québec, Canada.|Department of Microbiology, Infectious Diseases and Immunology, University of Montreal, Montréal, Québec, Canada.|Department of Medicine, University of Montreal, Montréal, Québec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D001854:Bone Marrow Cells / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C; D011119:Polynucleotides / Q000008:administration & dosage*; D014611:Vaccination
chemical_list: D019013:CD40 Antigens; D011119:Polynucleotides; D023201:CD40 Ligand; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011070:Poly I-C
keywords: CD40-activated B cells; CD8+; T cells; dendritic cells; effector and memory response; vaccination