PMID- 32580933 OWN - NLM STAT- MEDLINE DCOM- 20210315 LR - 20210315 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 205 IP - 3 DP - 2020 Aug 1 TI - Extracellular Release of Antigen by Dendritic Cell Regurgitation Promotes B Cell Activation through NF-kappaB/cRel. PG - 608-618 LID - 10.4049/jimmunol.1900394 [doi] AB - Dendritic cells (DCs) are professional APCs, which sample Ags in the periphery and migrate to the lymph node where they activate T cells. DCs can also present native Ag to B cells through interactions observed both in vitro and in vivo. However, the mechanisms of Ag transfer and B cell activation by DCs remain incompletely understood. In this study, we report that murine DCs are an important cell transporter of Ag from the periphery to the lymph node B cell zone and also potent inducers of B cell activation both in vivo and in vitro. Importantly, we highlight a novel extracellular mechanism of B cell activation by DCs. In this study, we demonstrate that Ag released upon DC regurgitation is sufficient to efficiently induce early B cell activation, which is BCR driven and mechanistically dependent on the nuclear accumulation of the transcription factor NF-kappaB/cRel. Thus, our study provides new mechanistic insights into Ag delivery and B cell activation modalities by DCs and a promising approach for targeting NF-kappaB/cRel pathway to modulate the DC-elicited B cell responses. CI - Copyright (c) 2020 by The American Association of Immunologists, Inc. FAU - El-Barbry, Houssam AU - El-Barbry H AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Capitao, Marisa AU - Capitao M AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Barrin, Sarah AU - Barrin S AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Amziani, Samir AU - Amziani S AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Pierre Paul, Pascal AU - Pierre Paul P AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Borreill, Susanna AU - Borreill S AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Guilbert, Thomas AU - Guilbert T AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Donnadieu, Emmanuel AU - Donnadieu E AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Niedergang, Florence AU - Niedergang F AUID- ORCID: 0000-0002-7064-830X AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France. FAU - Ouaaz, Fatah AU - Ouaaz F AUID- ORCID: 0000-0001-8881-5703 AD - Universite de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, F-75014 Paris, France fatah.ouaaz@inserm.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200624 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Antigens) RN - 0 (NF-kappa B) RN - 0 (Proto-Oncogene Proteins c-rel) SB - IM MH - Animals MH - *Antigen Presentation MH - Antigens/genetics/*immunology MH - B-Lymphocytes/*immunology MH - Dendritic Cells/*immunology MH - Female MH - *Lymphocyte Activation MH - Mice MH - Mice, Transgenic MH - NF-kappa B/genetics/*immunology MH - Proto-Oncogene Proteins c-rel/genetics/*immunology MH - Signal Transduction/*immunology EDAT- 2020/06/26 06:00 MHDA- 2021/03/16 06:00 CRDT- 2020/06/26 06:00 PHST- 2019/04/04 00:00 [received] PHST- 2020/05/03 00:00 [accepted] PHST- 2020/06/26 06:00 [pubmed] PHST- 2021/03/16 06:00 [medline] PHST- 2020/06/26 06:00 [entrez] AID - jimmunol.1900394 [pii] AID - 10.4049/jimmunol.1900394 [doi] PST - ppublish SO - J Immunol. 2020 Aug 1;205(3):608-618. doi: 10.4049/jimmunol.1900394. Epub 2020 Jun 24.