A5085662031- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Renal Diseases and Glomerulopathies
- Immunodeficiency and Autoimmune Disorders
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Cell death mechanisms and regulation
- Complement system in diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Platelet Disorders and Treatments
- HIV Research and Treatment
- Galectins and Cancer Biology
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- RNA regulation and disease
- Gastrointestinal Bleeding Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Microscopic Colitis
- Abdominal vascular conditions and treatments
- Glycosylation and Glycoproteins Research
- Vasculitis and related conditions
Inserm
2018-2025
Centre National de la Recherche Scientifique
2011-2025
Université de Limoges
2014-2025
Contrôle de la Réponse Immune B et Lymphoproliférations
2012-2025
Centre Hospitalier Universitaire de Limoges
2012
Hôpital Universitaire Dupuytren
2011
Laboratoire de Chimie Moléculaire
2005
Abstract Certain individuals are resistant to HIV-1 infection, despite repeated exposure the virus. Although protection against infection in a small proportion of Caucasian is associated with mutant alleles CCR5 coreceptor, molecular mechanism underlying resistance repeatedly HIV-1-exposed, uninfected (EU) unclear. In this study, we performed complementary transcriptome and proteome analyses on peripheral blood T cells, plasma or serum from EU, their HIV-1-infected sexual partners, healthy...
Abstract Immunoglobulin light chain (LC) amyloidosis (AL) is one of the most common types systemic but there no reliable in vivo model for better understanding this disease. Here, we develop a transgenic mouse producing human AL LC. We show that soluble full length LC not toxic single injection pre-formed amyloid fibrils or an unstable fragment leads to deposits associated with early cardiac dysfunction. mice are highly similar human, arguing conserved mechanism formation. Overall, closely...
ABSTRACT AL amyloidosis is one of the most common types systemic amyloidosis, caused by deposition in tissues fibrillar aggregates abnormal immunoglobulin (Ig) light chain (LC), leading to organ dysfunction. The frequent and severe forms affect kidneys heart, latter being associated with a poor prognosis. Despite extensive efforts decipher mechanisms fibril formation their toxicity, lack reliable vivo models hinders study disease its physiological context. We developped transgenic mouse...
// Alexis Saintamand 1 , Pauline Rouaud Armand Garot Faten Saad Claire Carrion Christelle Oblet Michel Cogné 1, 2, 3 Eric Pinaud Yves Denizot CNRS, CRIBL, UMR 7276, Limoges, France 2 Université de Institut Universitaire France, Paris, Correspondence to: Denizot, e-mail: yves.denizot@unilim.fr Keywords: BCR, B cell fate, IgH 3' regulatory enhancers, knock-out mice Received: December 17, 2014 Accepted: 21, Published: March 03, 2015 ABSTRACT We report that the region (3'RR) has no role on μ...
IgA1 mesangial deposition is the hallmark of IgA nephropathy and Henoch–Schönlein purpura, onset which often follows infections. Deposited has been reported as polymeric, J chain associated, often, hypogalactosylated but with no information concerning influence repertoire or link between immune stimuli structure. We explored these issues in α 1KI mouse model, produces polyclonal human prone to deposition. Compared mice challenged by a conventional environment, specific pathogen–free...
Objectives: The soluble HIV-1 gp120 envelope glycoprotein, after being shed from infected cells, can cross-link its receptors on both and non-infected target leading to their activation. We have assessed the impact of viral replication in CD4+/CXCR4+ T via effects Tat-mediated transactivation HIV-1/LTR. Materials methods: Primary cord blood-derived cells were stimulated with recombinant (rgp120) HIV-1/HXB2 clone. level gene or protein expression was by serial analysis (SAGE), reverse...
Significance Statement IgA nephropathy (IgAN) is characterized by glomerular mesangial deposition, but its pathogenesis remains unclear. Using humanized transgenic mouse models, the authors explored whether a hypogalactosylated hinge region (found in most IgA1 human IgAN) required for demonstrating that hypoglycosylation was not mandatory deposition. To investigate low-affinity produced innate-like B cells might also yield deposits, they compared mice able to produce high-affinity mature...
Activating mutations of MYD88 (MYD88L265P being the far most frequent) are found in cases Waldenström macroglobulinemia (WM) as well various aggressive B-cell lymphoma entities with features plasma cell (PC) differentiation, such activated type diffuse large (DLBCL). To understand how activation exerts its transformation potential, we developed a new mouse model which MYD88L252P protein, murine ortholog human MYD88L265P, is continuously expressed CD19 positive B-cells together Yellow...
Nerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in humoral response not well defined. Here, we study effect Ngfr loss on lymph node organization and function, demonstrating that depletion leads to spontaneous germinal center (GC) formation an expansion GC B cell compartment. In accordance with this effect, stromal are altered
Henoch-Schönlein purpura (HSP) and IgA nephropathy (IgAN) are characterized by mesangial deposition of polyclonal eventually showing aberrant glycosylation, affinity for cells and/or co-precipitation with antigen, bacterial peptides, autoantibodies or soluble receptors. were also suggested to be negatively charged predominantly λ type but rarely in a monoclonal form.A gammopathy case HSP provided us unique molecularly defined nephritogenic IgA1λ. Immunological analysis, biological...
Deregulation of c-myc by translocation onto immunoglobulin (Ig) loci can promote B cell malignant proliferations with phenotypes as diverse acute lymphoid leukemia, Burkitt lymphoma, diffuse large myeloma... The receptor (BCR) normally providing tonic signals for survival and mitogenic responses to antigens, also contribute lymphomagenesis upon sustained ligand binding or activating mutations. BCR signaling varies among compartments classes. For unknown reasons, some malignancies associate...
Fanconi syndrome (FS) is a rare renal disorder featuring proximal tubule dysfunction that may occur following tubular reabsorption of monoclonal light chain (LC), in patients with multiple myeloma. FS precede the recognition myeloma by several years. In most cases, crystalline inclusions κ LCs are observed within lysosomes cells (PTCs) and probably participate their functional alteration. To investigate mechanism implicated dysfunction, we compared effects LC-CHEB obtained from patient...
Introduction In mature B cells, activation-induced deaminase reshapes Ig genes through somatic hypermutation and class switch recombination of the heavy chain ( IgH ) locus under control its 3’ cis -regulatory region 3’RR ). The is itself transcribed can undergo “locus suicide recombination” (LSR), then deleting constant gene cluster terminating expression. relative contribution LSR to cell negative selection remains be determined. Methods Here, we set up a knock-in mouse reporter model for...
Upregulated expression of the anti-apoptotic BCL2 oncogene is a common feature various types B-cell malignancies, from lymphoma to leukemia or myeloma. It currently unclear how patterns deregulation observed in pathology eventually impact phenotype malignant B cells and their microenvironment. Follicular (FL) most non-Hodgkin arising germinal center (GC) B-cells, its major hallmark t(14:18) translocation occurring cell progenitors placing gene under control immunoglobulin heavy chain locus...
Abstract CD95 is a death receptor that can promote oncogenesis through molecular mechanisms are not fully elucidated. Although the mature membrane considered to start with arginine at position 17 after elimination of signal peptide, this also be cleaved by MMP7 upstream its leucine 37. This post-translational modification occurs in cancer cells but normal such as peripheral blood leukocytes. The non-cleaved amino-terminal region consists disordered domain and silico reconstitution suggests...
Abstract The expression of the Nerve growth factor receptor (NGFR) has been described in follicular dendritic cells (FDCs), major lymphoid stromal cell (LSC) compartment regulating B-cell activation within germinal centers (GCs). However, role NGFR humoral response is not well defined. In this work, we have studied effect Ngfr KO LNs organization and function. led to spontaneous GC formation expansion which were related depletion non-hematopoietic radioresistant compartment. agreement, mice...
Abstract To better understand the stoichiometry of CD95L required to trigger apoptotic and nonapoptotic signals, we generated several concatemers from dimer hexamer conjugated via a flexible link (GGGGS) 2 . These ligands reveal that although hexameric structure is best cell death, sufficient induce response in CD95‐sensitive Jurkat cells. Interestingly, only trimeric forms can implement potent Ca 2+ response, suggesting while CD95 aggregation controls implementation signal, both...