A5044719453- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Renal Transplantation Outcomes and Treatments
- Immunotherapy and Immune Responses
- Mosquito-borne diseases and control
- Viral Infections and Vectors
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- Vector-borne infectious diseases
- CRISPR and Genetic Engineering
- Research on Leishmaniasis Studies
- Monoclonal and Polyclonal Antibodies Research
- Trypanosoma species research and implications
- SARS-CoV-2 and COVID-19 Research
- IL-33, ST2, and ILC Pathways
- Parasites and Host Interactions
- Adipokines, Inflammation, and Metabolic Diseases
- Virology and Viral Diseases
- Diabetes and associated disorders
- Hematopoietic Stem Cell Transplantation
- Neurogenetic and Muscular Disorders Research
- Lymphatic System and Diseases
- Influenza Virus Research Studies
- Renal Diseases and Glomerulopathies
- Genomic variations and chromosomal abnormalities
Harvard University
2020-2025
Brigham and Women's Hospital
2020-2025
Boston Children's Hospital
2024
Universidade Federal do Rio de Janeiro
2016-2022
Rockefeller University
2017-2021
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
2017-2018
Repeated exposure to pathogens or their antigens triggers anamnestic antibody responses that are higher in magnitude and affinity than the primary response. These involve reengagement of memory B cell (MBC) clones, diversity specificity which determine breadth effectiveness ensuing Using prime-boost models mice, we find secondary characterized by a clonality bottleneck restricts engagement large MBC clones generated priming. Rediversification mutated MBCs is infrequent within germinal...
Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although against SARS-CoV-2 based on mRNA adenoviral vector technologies have been rapidly developed, additional practical scalable are required meet global demand. Protein subunit formulated with appropriate adjuvants represent an approach address this urgent need. The receptor binding domain (RBD) a key...
Follicular helper T (Tfh) cells promote, whereas follicular regulatory (Tfr) restrain, germinal center (GC) reactions. However, the precise roles of these in complex GC reaction remain poorly understood. Here, we perturb Tfh or Tfr after SARS-CoV-2 spike protein vaccination mice. We find that promote frequency and somatic hypermutation (SHM) Spike-specific B regulate clonal diversity. similarly control SHM diversity but do so by limiting competition. In addition, deletion during primary...
Protective adaptive immunity to Zika virus (ZIKV) has been mainly attributed cytotoxic CD8+ T cells and neutralizing antibodies, while the participation of CD4+ in resistance remained largely uncharacterized. Here, we show a antibody response, dependent on IFNγ signaling, which detected during first week infection is associated with reduced viral load brain, prevention rapid disease onset survival. We demonstrate these components ZIKV primary murine adoptive transfer models heterologous...
Follicular helper T (Tfh) cells are essential for the formation of high affinity antibodies after vaccination or infection. Although signals responsible initiating Tfh differentiation from naïve have been studied, controlling sequential developmental stages culminating in optimal effector function not well understood. Here we use fate mapping strategies cytokine IL-21 to uncover including a progenitor-like stage, fully developed stage and post-effector that maintains transcriptional...
Follicular helper T (Tfh) cells have been implicated in controlling rejection after allogeneic kidney transplantation, but the precise subsets, origins, and functions of Tfh this process not fully characterized. Here we show that a subset effector marked by previous IL-21 production is potently induced during transplantation inhibited immunosuppressive agents. Single-cell RNA-Seq revealed these lymph node (LN) transcriptional clonal overlap with IL-21-producing kidney-infiltrating cells,...
Pathogenic antibodies produced by alloreactive B cells mediate antibody-mediated rejection after kidney transplantation, but the mechanisms remain poorly understood. Follicular regulatory T (Tfr) modulate follicular helper cell-mediated cell responses, functions of Tfr in controlling antibody are unknown. Here we study developmental signals and mouse allogeneic transplantation models, show that costimulatory blockade alters development disproportionately decreasing germinal center (GC)-like...
Humoral immunity is orchestrated by follicular helper T (Tfh) cells, which promote cognate B cells to produce high-affinity, protective antibodies. In aged individuals, humoral after vaccination diminished despite the presence of Tfh suggesting defects initial formation. this study, we utilized both murine and human systems investigate how aging alters cell differentiation influenza vaccination. We found that young underwent progressive vaccination, culminating in clonal expansion...
Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue Zika infections have been linked antibody-mediated autoimmune disorders, including Guillain-Barré syndrome. A unique feature of flaviviruses is the secretion nonstructural protein 1 (NS1) by infected cells. NS1 highly immunogenic, antibodies targeting both protective pathogenic roles. In present study, we investigated found be an...
Background. Following allogeneic kidney transplantation, a substantial proportion of graft loss is attributed to the formation donor-specific antibodies and antibody-mediated rejection. B cells infiltrate grafts during rejection; however, origins, repertoires, functions these intrarenal remain elusive. Methods. Here, we use murine transplant models study transcriptional programming cell receptor repertoire intragraft cells, in vitro stimulation assays evaluate ability promote CD4+ T...
BACKGROUND: Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in CALM1 , CALM2 or CALM3 which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)–mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas other 2 genes preserve level and function. METHODS: tested this hypothesis using human induced pluripotent stem cell–derived cardiomyocyte mouse...
We developed a method for rapid generation of B cell receptor (BCR) monoclonal mice expressing prerearranged Igh and Igk chains monoallelically from the locus by CRISPR-Cas9 injection into fertilized oocytes. cells these undergo somatic hypermutation (SHM), class switch recombination (CSR), affinity-based selection in germinal centers. This combines practicality BCR transgenes with ability to study Ig SHM, CSR, affinity maturation.
Although donor-specific antibody pre- and posttransplantation is routinely assessed, accurate quantification of memory alloreactive B cells that mediate recall response remains challenging. Major histocompatibility complex (MHC) tetramers have been used to identify in mice humans, but the specificity this approach has not rigorously assessed.
Lymph node (LN)-resident stromal cells play an essential role in the proper functioning of LNs. The compartment LN undergoes significant compensatory changes to produce a milieu amenable for regulation immune response. We have identified distinct population leptin receptor-expressing (LepR + ) cells, located vicinity high endothelial venules (HEVs) and lymphatics. These LepR expressed markers fibroblastic reticular (FRCs), but they lacked follicular dendritic (FDCs) marginal (MRCs). Leptin...
Natural antibodies (NAbs) are produced in the absence of exogenous antigenic stimulation and circulate blood normal, healthy individuals. These have been shown to provide one first lines defense against both bacterial viral pathogens. Conservation NAb repertoire reactivity profile is observed within across species. One view holds that this conservation self reactivities reflects use germline antibody sequence, whereas opposing self-reactivities reflect selection driven by key conserved...
Abstract Background and Aims Systemic lupus erythematosus (SLE) is an autoimmune disorder in which autoantibody formation can lead to severe kidney pathology. Interleukin (IL)17-producing T cells have been suggested play important role the pathogenesis of SLE, IL-17 inhibition was shown ameliorate SLE pathology lupus-prone mice. Moreover, frequency circulating follicular helper (Tfh) cells, a cell subset that orchestrates maturation high-affinity antibodies germinal center secondary lymphoid...
Introduction: Antisense Oligonucleotides (ASOs) are an emerging class of drugs that target RNAs to impede their production, stability, and translation. Calmodulinopathies severe cardiac arrhythmias caused by dominant mutations in CALM1 , CALM2 or CALM3 . Each these genes encodes the identical calmodulin (CaM) protein. Leveraging this genetic redundancy, we hypothesized ASO-mediated knockdown affected CALM gene would treat arrhythmia while functional redundancy other maintain CaM protein...
Graft-versus-host disease (GVHD) is the main complication of bone marrow transplantation (BMT). CD4+ T lymphocytes are effector cells for development, but other cell types can determine outcome through cytokine production and antigen presentation. B abundant in BMT products involved chronic GVHD immunopathogenesis. However, their role acute still unclear. Here we studied donor resting a model GVHD. Animals receiving transplants depleted developed more severe disease, indicating protective...
We developed a method for rapid generation of B cell receptor (BCR) monoclonal mice expressing pre-rearranged Igh and Igk chains monoallelically from the locus by CRISPR/Cas9 injection into fertilized oocytes. cells these undergo somatic hypermutation (SHM), class switch recombination (CSR), affinity-based selection in germinal centers. This combines practicality BCR transgenes with ability to study Ig SHM, CSR affinity maturation.