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    After eating by macropinocytosis, dendritic cells regurgitate unprocessed antigen to activate B cells

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    Florence Niedergang team

    After eating by macropinocytosis, dendritic cells regurgitate unprocessed antigen to activate B cells.

     

    A recent study carried out under the direction of Fatah Ouaaz within the “Biology of phagocytes, Infection & Immunity” team, highlights a novel extracellular mechanism of B-cell activation by dendritic cell regurgitation of antigen through the nuclear mobilization of the transcription factor NF-kB/cRel. This work has been published on July 2020 in The Journal of Immunology.

     

    Dendritic cells (DCs) are professional phagocytic cells that sample antigens (Ags) in the periphery and migrate to lymph nodes (LNs) where they present them to T lymphocytes for initiating T-cell immunity. Humoral immunity is essential for protection against cancer and infections by generating high affinity antibodies that neutralize pathogens in peripheral tissues. The initiation of the humoral response occurs mainly within the follicular region of LNs, where B cells recognize their cognate Ag in its “native” form in contrast to T cells which recognize “degraded” Ags. However, the mechanisms of Ag transfer and the direct B-cell activation by DCs remain incompletely understood.

     

     

    By using a subcutaneous delivery of Ag-pulsed DCs in vivo and imaging by confocal microscopy, first the authors visualized the trafficking of Ag-loaded DCs from the periphery to the LN paracortex followed by a strategic repositioning within the follicular B-cell zone. By using this in vivo approach and also an in vitro co-culture system, they report that DCs are not only peripheral carriers of Ag but also potent B-cell activators both in vivo and in vitro.They highlight that Ag released by DC regurgitation was sufficient to efficiently induce early B-cell activation, which was BCR-driven and mechanistically dependent on the nuclear mobilization of NF-kB/cRel. 

     

     

     

     

     

    By blocking cRel by chemical inhibition with pentoxifylline (PTXF), the authors showed that PTXF treatment impaired cRel expression and early B-cell activation induced exclusively following BCR stimulation with HEL but not through TLR4 stimulation with microbial LPS. The key role of cRel in the Ag-dependent early B-cell activation suggests that drug inhibition of this NF-kB member would represent a promising strategy to restrain the excessive DC-elicited B-cell responses in auto-immunity without altering the host humoral defense against bacterial infections.

     

    Thus, our study provides new mechanistic insights into Ag delivery and B-cell activation by DCs and a promising approach for targeting NF-kB/c-Rel pathway to modulate the DC-elicited B-cell responses. 

     

    Further information

    Extracelluar release of antigen by dendric cell regurgitation promotes B-cell activation through NF-kB/cRel.  El-Barbry H*, Capitao M*, Barrin S, Amziani S, Pierre-Paul P, Borreill S, Guilbert T, Donnadieu E, Niedergang F* and Ouaaz F*.   J. Immunol. July 2020.  doi: 10.4049/jimmunol.1900394

     

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