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Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2018
Renseignements relatifs à l’Unité de Recherche :
Label et intitulé : INSERM U1016 - CNRS UMR 8104 - Université Paris Descartes
Nom et prénom du Directeur : Dr. COURAUD Pierre Olivier
Téléphone :
01 40 51 64 57
Télécopie : 01 40 51 64 73
Courriel: [email protected]
Renseignements relatifs à l’Equipe :
Nom de l’Equipe d’Accueil : Biologie des Phagocytes
Nom et prénom du responsable : Dr. NIEDERGANG Florence
Qualité du responsable : Directeur de recherches CNRS (DR1)
Téléphone :
01 40 51 64 21
Télécopie : 01 40 51 64 30
Courriel : [email protected]
Renseignements relatifs au sujet de thèse :
Nom et prénom du Directeur de thèse (HDR) : Dr OUAAZ Fatah
Qualité : Chargé de recherches INSERM (CR1)
Téléphone :
01 40 51 64 51
Télécopie : 01 40 51 64 54
Courriel : [email protected]
Titre du sujet proposé :
(En français) : Rôle des cellules dendritiques dans le transport et le transfert de l’antigène aux
lymphocytes B et dans l’initiation de la réponse humorale in vivo.
(En anglais) : Role of dendritic cells in antigen transport and transfer to B cells and in the initiation of
the humoral response in vivo.
Département (cocher le département correspondant au sujet de thèse qui n’est pas obligatoirement le
vôtre) :
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Biologie Cellulaire et moléculaire, Physiologie et Physiopathologie
Immunologie
Développement Génétique Neurobiologie et Vieillissement
Infectiologie, Microbiologie
Summary (5 lines maximum) :
Antigen recognition by B cells occurs in secondary lymphoid organs and leads to activation, expansion and differentiation of
B cells into memory or antibody secreting plasma cells. The objective of this project is to unravel the role of dendritic cells
(DCs) in antigen transport to lymph node B cells and the impact of this Ag delivery path on the initiation of the humoral
immune response. The role of DC subsets in antigen transport, transfer, B-cell activation and the underlying mechanisms will
be investigated in vivo and in co-cultures in vitro.
Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2087
(L’ensemble de cette fiche ne doit pas dépasser 1 page)
Nom, prénom du directeur de l'unité de recherche : Dr. COURAUD Pierre Olivier
Numéro de l'unité de recherche (et établissement de rattachement) : INSERM U1016 - CNRS UMR
8104 - Université Paris Descartes
Nom, prénom du responsable de l'équipe d'accueil (EAD) : Dr. NIEDERGANG Florence
Nom, prénom du directeur de thèse : Dr. OUAAZ Fatah
Titre du sujet de thèse proposé :
(en anglais) Role of dendritic cells in antigen transport and transfer to B cells and in the initiation of the
humoral response in vivo.
Citer 5 mots clés : Dendritic cell, B lymphocyte, antigen, antibody, lymph node
(key words)
Candidat pressenti : 
OUI
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NON
Contenu scientifique du programme de la thèse (en anglais)
Antibody-producing B lymphocytes are the major arm of the adaptive humoral immunity. B cells home to the secondary
lymphoid organs where they recognize their cognate native antigen (Ag). However, the mechanism of antigen encounter by
B cells still remains unclear. Our previous findings propose that dendritic cells (DCs) are one major Ag cell transporter to B
cells from the periphery to the lymph node (LN). It was also highlighted in DCs a possibility of an extracellular release of
native Ag from late endosomes that is regulated by the small GTPase Rab27 and that was called “regurgitation”. More
recently, we have shown the ability of HEL (Ag model) loaded-DCs to migrate to the LN and to activate B cell polyclonal
responses in vivo.
On the basis of these findings, the PhD candidate will now explore: 1) the in vivo impact of Ag-loaded DCs on the spatiotemporal B cell activation, B cell memory generation and antibody response; 2) the respective roles of the migratory vs LN
resident-DCs in Ag transport and transfer to LN B cells and in the subsequent B-cell activation; 3) the intracellular
mechanisms underlying Ag transfer and B cell activation by DCs by investigating the role of Rab27 in Ag transfer and the
NF-B pathway in B cell activation.
The PhD candidate will use murine specific anti-HEL B cells (MD4 transgenic mice) and DCs (bone marrow-derived
DCs; ex vivo purified spleen DC subsets) to explore the in vivo traffic of Ag, and the mechanisms of Ag transfer and B cell
activation in vivo but also in DCs-B cells co-culture in vitro by using multi-color flow cytometry, immuno-histochemistry and
both confocal and intravital microscopy. He/she will also measure by ELISA antibody production in mice sera following
immunization with HEL-loaded DCs. NF-B activation will be analyzed after cytosolic / nuclear extracts preparation followed
by EMSA and western blotting. All experimental approaches are available in the laboratory. We expect to provide new
insights into antigen encounter by B cells in vivo and also new approaches for DC targeting to elicit humoral immunity.
Indiquez les cinq meilleures publications récentes de l’équipe :
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Dumas A, Lê-Bury G, Marie-Anaïs F, Herit F, Mazzolini J, Guilbert T, Bourdoncle P., Russell DG, Benichou S, Zahraoui A, and
Niedergang F (2015). The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking. J. Cell
Biol. 211 : 359-372
Le Roux D, Le Bon A, Dumas A, Taleb K, Sachse M, Sikora R, Julithe M, Benmerah A, Bismuth G, Niedergang F. (2012). Antigen
stored in dendritic cells after macropinocytosis is released unprocessed from late endosomes to target B cells. Blood. 119, 95-105.
Marion S, Mazzolini J, Herit F, Bourdoncle P,Kambou-Pene N, Hailfinger S, Sachse M, Benmerah A, Echard A, Thome M and
Niedergang F (2012). The NF-B signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles.
Dev Cell. 23 : 954-967.
Courtine E, Cagnard N, Mazzolini J, Antona M, Pène F, Fitting C, Jacques S, Rousseau C, Niedergang F, Gerondakis S, Chiche
JD, Ouaaz F#, Mira JP# (2012). Combined loss of cRel/p50 subunits of NF-B leads to impaired innate host response in sepsis. Inn
Immun. 18 :753-763 (* co-last authors).
Courtine E, Frédéric Pène, Nicolas Cagnard, Julie Toubiana ,, Catherine Fitting, Jessy Brocheton, Christophe Rousseau, Steve
Gerondakis, Jean-Daniel Chiche, Fatah Ouaaz*, and Jean-Paul Mira* (2011). Critical role of cRel subunit of NF-B in sepsis
survival. Infect Immun. 79, 1848-1854 (* co-last authors).