Extracellular Release of Antigen by Dendritic Cell Regurgitation Promotes B Cell Activation through NF-κB/cRel

J Immunol. 2020 Aug 1;205(3):608-618. doi: 10.4049/jimmunol.1900394. Epub 2020 Jun 24.

Abstract

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-κB/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-κB/cRel pathway to modulate the DC-elicited B cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigens / genetics
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • NF-kappa B / genetics
  • NF-kappa B / immunology*
  • Proto-Oncogene Proteins c-rel / genetics
  • Proto-Oncogene Proteins c-rel / immunology*
  • Signal Transduction / immunology*

Substances

  • Antigens
  • NF-kappa B
  • Proto-Oncogene Proteins c-rel