A5065384160- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Heat shock proteins research
- Cancer-related gene regulation
- Transgenic Plants and Applications
- Epigenetics and DNA Methylation
- Toxin Mechanisms and Immunotoxins
- RNA modifications and cancer
- Magnesium in Health and Disease
- Nanoparticles: synthesis and applications
- Endoplasmic Reticulum Stress and Disease
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Diabetes and associated disorders
- IL-33, ST2, and ILC Pathways
- Graphene and Nanomaterials Applications
- Trypanosoma species research and implications
Montreal Clinical Research Institute
2015-2023
University Hospital of Basel
2020-2022
University of Basel
2020-2021
Université de Montréal
2015
Analysis of CD4 + T cell heterogeneity in the lung uncovers a Bcl6-dependent subset that supports mucosal antibody production.
CD4+ memory T cells play an important role in protective immunity and are a key target vaccine development. Many studies have focused on central (Tcm) cells, whereas the existence functional significance of long-lived follicular helper (Tfh) controversial. Here, we show that Tfh highly susceptible to NAD-induced cell death (NICD) during isolation from tissues, leading their underrepresentation prior studies. NICD blockade reveals persistence abundant with high expression hallmark markers at...
Mechanisms regulating B cell development, activation, education in the germinal center (GC) and differentiation, underpin humoral immune response. Protein arginine methyltransferase 5 (Prmt5), which catalyzes most symmetric dimethyl protein modifications, is overexpressed lymphomas but its function normal cells poorly defined. Here we show that Prmt5 necessary for antibody responses has essential distinct functions all proliferative stages mice. development by preventing p53-dependent...
Abstract Activation-induced deaminase (AID) mutates the immunoglobulin ( Ig ) genes to initiate somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, thus underpinning antibody responses. AID a few hundred other loci, but most AID-occupied are spared. The mechanisms underlying productive deamination versus non-productive targeting unclear. Here we show that three clustered arginine residues define functional domain required for SHM, CSR, off-target activity cells...
Activation-induced deaminase (AID) initiates mutagenic pathways to diversify the antibody genes during immune responses. The access of AID nucleus is limited by CRM1-mediated nuclear export and an uncharacterized mechanism cytoplasmic retention. Here, we define a conformational motif in that dictates its retention demonstrate translation elongation factor eukaryotic 1 α (eEF1A) necessary for sequestering. independent protein synthesis but dependent on tRNA-free form eEF1A. Inhibiting eEF1A...
Activation induced deaminase (AID) initiates somatic hypermutation and class switch recombination of the Ig genes in antigen-activated B cells, underpinning antibody affinity maturation isotype switching. AID can also be pathogenic by contributing to autoimmune diseases oncogenic mutations. Moreover, exert noncanonical functions when aberrantly expressed epithelial cells. The lack specific inhibitors prevents therapeutic applications modulate functions. Here, we have exploited our previous...
Positively selected germinal center B cells (GCBC) can either resume proliferation and somatic hypermutation or differentiate. The mechanisms dictating these alternative cell fates are incompletely understood. We show that the protein arginine methyltransferase 1 (Prmt1) is upregulated in murine GCBC by Myc mTORC-dependent signaling after positive selection. Deleting Prmt1 activated compromises antibody affinity maturation hampering light zone to dark cycling. deficiency also results...
Abstract Influenza is a severe and acute respiratory pathogen, significant cause for morbidity, particularly in young children the elderly. Following influenza infection, clonally expanded T cells take up permanent residence lung where they are poised to rapidly respond challenge infection. The non-circulating status of these tissue resident memory (TRM) makes them an attractive target vaccination. While many studies have characterized CD8 TRM cells, less known about heterogeneity protective...
The enzyme Activation induced deaminase (AID) underpins antibody affinity maturation and isotype switching through its mutagenic activity of deaminating deoxycytidine to deoxyuridine in DNA. Subsequent processing the initiates processes somatic hypermutation (SHM) class switch recombination (CSR) B cells. Structure-function analysis AID requires sensitive biologically relevant methods measure various activities. Here we describe simple but effective 1) ability mutate Escherichia coli genome,...