Dendritic cells (DCs) are professional phagocytic cells, well known for their efficient capture of material by macropinocytosis in the periphery and presentation of antigen (Ag) to T lymphocytes in the lymph node (LN). In contrast to macrophages, DCs display non-degradative intracellular compartments that allow them to store the internalized Ag in its native form. We previously described in DCs an original mechanism of recycling to the extracellular milieu of non-degraded material from late endocytic compartments that we called “regurgitation”(Le Roux et al., 2012).
Recently, we showed that DCs are a major cell transporter of Ag from the periphery to the B-cell zone of the lymph nodes and potent B-cell activators both in vivo and in vitro. We highlighted also a new extracellular mode of Ag-dependent B-cell activation by DCs. We demonstrated 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-kB/cRel (El-Barbry et al., 2020). We investigate now regurgitation by the distinct DCs subsets and the molecular mechanisms controlling and modulating this process in DCs. We will also explore how viral infection may affect DC regurgitation and subsequently impact early B cell activation.
Our findings reveal a unique property of DCs as they are equipped with both non-degradative and degradative Ag uptake pathways to perform Ag presentation to both B and T cells, making these APCs as an interesting and potential cellular platform for efficient vaccination.
- Le Roux, D., Le Bon, A., Dumas, A., Taleb, K., Sachse, M., Sikora, R., Julithe, M., Benmerah, A., Bismuth, G., and Niedergang, F. (2012). Antigen stored in dendritic cells after macropinocytosis is released unprocessed from late endosomes to target B cells. Blood 119, 95-105.
- El-Barbry, H., Capitao, M., Barrin, S., Amziani, S., Pierre-Paul, P., Borreill, S., Guilbert, T., Donnadieu, E., Niedergang, F*, and Ouaaz, F*. Extracellular release of antigen by dendritic cell regurgitation promotes B cell activation through NF-κB/cRel. The Journal of Immunology (2020), 205:608-618
- Le Roux, D., and Niedergang, F. (2012). New insights into antigen encounter by B cells. Immunobiology 217, 1285-1291. Review.
- Hedia Hebibi , Marvin Edeas, Laure Cornillac, Severine Beaudreuil, Jedjiga Achiche, David Attaf, Samah Saibi, Charles Chazot, Fatah Ouaaz † and Bernard Canaud †. SARS-CoV-2 mRNA Vaccine Immunogenicity in Hemodialysis Patients: Promising Vaccine Protection That May Be Hindered by Fluid Overload. Kidney Dial (2022), 2:44–56.