title: In vitroandin vivoimaging of initial B-T-cell interactions in the setting of B-cell based cancer immunotherapy.
abstract: There has been a growing interest in the use of B cells for cancer vaccines, since they have yielded promising results in preclinical animal models. Contrary to dendritic cells (DCs), we know little about the migration behavior of B cellsin vivo. Therefore, we investigated the interactions between CD40-activated B (CD40B) cells and cytotoxic T cellsin vitroand the migration behavior of CD40B cellsin vivo. Dynamic interactions of human antigen-presenting cells (APCs) and T cells were observed by time-lapse video microscopy. The migratory and chemoattractant potential of CD40B cells was analyzedin vitroandin vivousing flow cytometry, standard transwell migration assays, and imaging of fluorescently labeled murine CD40B cells. Murine CD40B cells show migratory features similar to human CD40B cells. They express important lymph node homing receptors which were functional and induced chemotaxis of T cellsin vitro. Striking differences were observed with regard to interactions of human APCs with T cells. CD40B cells differ from DCs by displaying a rapid migratory pattern undergoing highly dynamic, short-lived and sequential interactions with T cells.In vivo, CD40B cells are home to the secondary lymphoid organs where they accumulate in the B cell zone before traveling to the B/T cell boundary. Moreover, intravenous (i.v.) administration of murine CD40B cells induced an antigen-specific cytotoxic T cell response. Taken together, this data show that CD40B cells home secondary lymphoid organs where they physically interact with T cells to induce antigen-specific T cell responses, thus underscoring their potential as cellular adjuvant for cancer immunotherapy.
authors.affiliation: Department of Hematology; Vall d'Hebron University Hospital; VHIR; Universitat Autónoma de Barcelona ; Barcelona, Spain ; Cologne Interventional Immunology (CII); University Hospital of Cologne ; Cologne, Germany ; Department I of Internal Medicine; University Hospital of Cologne ; Cologne, Germany.
authors.forename: Nela Klein
authors.initials: NK
authors.lastname: Gonzalez
authors.affiliation: Cologne Interventional Immunology (CII); University Hospital of Cologne ; Cologne, Germany ; Department I of Internal Medicine; University Hospital of Cologne ; Cologne, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wennhold
authors.affiliation: Department of Dermatology and Research Center for Immunology (FZI); University Medical Center Mainz ; Mainz, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Balkow
authors.affiliation: Department of General Medicine; Okayama University ; Okayama, Japan.
authors.forename: Eisei
authors.initials: E
authors.lastname: Kondo
authors.affiliation: Institute of Cardiology and Sports Medicine; Department of Molecular and Cellular Sport Medicine; German Sport University Cologne ; Cologne, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Bölck
authors.affiliation: Cologne Interventional Immunology (CII); University Hospital of Cologne ; Cologne, Germany ; Department I of Internal Medicine; University Hospital of Cologne ; Cologne, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Weber
authors.affiliation: Cologne Interventional Immunology (CII); University Hospital of Cologne ; Cologne, Germany ; Department I of Internal Medicine; University Hospital of Cologne ; Cologne, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Garcia-Marquez
authors.affiliation: Department of Dermatology and Research Center for Immunology (FZI); University Medical Center Mainz ; Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.affiliation: Institute of Cardiology and Sports Medicine; Department of Molecular and Cellular Sport Medicine; German Sport University Cologne ; Cologne, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.affiliation: Cologne Interventional Immunology (CII); University Hospital of Cologne ; Cologne, Germany ; Department I of Internal Medicine; University Hospital of Cologne ; Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: von Bergwelt-Baildon
authors.affiliation: Cologne Interventional Immunology (CII); University Hospital of Cologne ; Cologne, Germany ; Department I of Internal Medicine; University Hospital of Cologne ; Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
keywords: CD40-activated B cells; antigen presentation; cancer immunotherapy; cellular adjuvant; migration