Essential role of membrane cholesterol in accelerated BCR internalization and uncoupling from NF-κB in B cell clonal anergy

Divergent hypotheses exist to explain how signaling by the B cell receptor (BCR) is initiated after antigen binding and how it is qualitatively altered in anergic B cells to selectively uncouple from nuclear factor κB and c-Jun N-terminal kinase pathways while continuing to activate extracellular signal–regulated kinase and calcium–nuclear factor of activated T cell pathways. Here we find that BCRs on anergic cells are endocytosed at a very enhanced rate upon binding antigen, resulting in a large steady-state pool of intracellularly sequestered receptors that appear to be continuously cycling between surface and intracellular compartments. This endocytic mechanism is exquisitely sensitive to the lowering of plasma membrane cholesterol by methyl-β-cyclodextrin, and, when blocked in this way, the sequestered BCRs return to the cell surface and RelA nuclear accumulation is stimulated. In contrast, when plasma membrane cholesterol is lowered and GM1 sphingolipid markers of membrane rafts are depleted in naive B cells, this does not diminish BCR signaling to calcium or RelA. These results provide a possible explanation for the signaling changes in clonal anergy and indicate that a chief function of membrane cholesterol in B cells is not to initiate BCR signaling, but instead to terminate a subset of signals by rapid receptor internalization

EVALUATION OF THE NEWLY FORMED BONE IN IRRADIATED AREAS BY ADDITION OF MESENCHYMAL STEM CELLS TO THE ASSOCIATION OF BIPHASIC CALCIUM PHOSPHATE AND TOTAL BONE MARROW

Oral Communication presented at the ";Forum des Jeunes Chercheurs";, Brest (France) 2011

The Role of Natural Killer Cells in Sepsis

Severe sepsis and septic shock are still deadly conditions urging to develop novel therapies. A better understanding of the complex modifications of the immune system of septic patients is needed for the development of innovative immunointerventions. Natural killer (NK) cells are characterized as CD3−NKp46+CD56+ cells that can be cytotoxic and/or produce high amounts of cytokines such as IFN-γ. NK cells are also engaged in crosstalks with other immune cells, such as dendritic cells, macrophages, and neutrophils. During the early stage of septic shock, NK cells may play a key role in the promotion of the systemic inflammation, as suggested in mice models. Alternatively, at a later stage, NK cells-acquired dysfunction could favor nosocomial infections and mortality. Standardized biological tools defining patients' NK cell status during the different stages of sepsis are mandatory to guide potential immuno-interventions. Herein, we review the potential role of NK cells during severe sepsis and septic shock

Crystal Structure of the C-type Lectin-like Domain from the Human Hematopoietic Cell Receptor CD69

CD69, one of the earliest specific antigens acquired during lymphoid activation, acts as a signal-transducing receptor involved in cellular activation events, including proliferation and induction of specific genes. CD69 belongs to a family of receptors that modulate the immune response and whose genes are clustered in the natural killer (NK) gene complex. The extracellular portion of these receptors represent a subfamily of C-type lectin-like domains (CTLDs), which are divergent from true C-type lectins and are referred to as NK-cell domains (NKDs). We have determined the three-dimensional structure of human CD69 NKD in two different crystal forms. CD69 NKD adopts the canonical CTLD fold but lacks the features involved in Ca(2+) and carbohydrate binding by C-type lectins. CD69 NKD dimerizes noncovalently, both in solution and in crystalline state. The dimer interface consists of a hydrophobic, loosely packed core, surrounded by polar interactions, including an interdomain beta sheet. The intersubunit core shows certain structural plasticity that may facilitate conformational rearrangements for binding to ligands. The surface equivalent to the binding site of other members of the CTLD superfamily reveals a hydrophobic patch surrounded by conserved charged residues that probably constitutes the CD69 ligand-binding site.Fil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Viedma, Fernando. Universidad Autónoma de Madrid; EspañaFil: Sánchez Madrid, Francisco. Universidad Autónoma de Madrid; EspañaFil: Tormo, José. Universidad Autónoma de Madrid; Españ

CIN85 drives B cell responses by linking BCR signals to the canonical NF-κB pathway

CIN85 transduces B cell receptor signals to IKK-β, and its expression in B cells is essential for T cell–independent type II antibody responses in mice

Inhibitory signaling blocks activating receptor clustering and induces cytoskeletal retraction in natural killer cells

Signaling from immunotyrosine-based inhibitory motifs (ITIMs) neutralizes activating signals by inducing a retraction of NK cells from the surface of stimulatory cells

Communication par voie électronique en appel (sans représentation obligatoire) : un régime réglementaire inachevé

International audienc

Décret n° 2005-460 du 13 mai 2005 relatif aux compétences des juridictions civiles, à la procédure civile et à l'organisation judiciaire

International audienc

Réforme de la procédure civile : simplification des exceptions d’incompétence: Décr. n° 2019-1333, 11 déc. 2019, JO 12 déc.

Commentaire d'arrêtNational audienceLe décret n° 2019-1333 du 11 décembre 2019 réformant la procédure civile a été publié au Journal officiel du 12 décembre. Il simplifie les exceptions d’incompétence au sein d’un même tribunal judiciaire en permettant un renvoi devant le juge compétent avant la première audience par simple mention au dossier