162 results match your criteria: "Gwen Knapp Center for Lupus and Immunology Research[Affiliation]"
Proc Natl Acad Sci U S A
February 2020
Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029;
While single-cell sequencing technologies have revealed tissue heterogeneity, resolving mixed cellular libraries into cellular clones is essential for many pooled screens and clonal lineage tracing. Fluorescent proteins are limited in number, while DNA barcodes can only be read after cell lysis. To overcome these limitations, we used influenza virus hemagglutinins to engineer a genetically encoded cell-surface protein barcoding system.
View Article and Find Full Text PDFNat Commun
October 2019
Department of Pathology, New York University School of Medicine, New York University, New York, NY, USA.
B-1a cells are long-lived, self-renewing innate-like B cells that predominantly inhabit the peritoneal and pleural cavities. In contrast to conventional B-2 cells, B-1a cells have a receptor repertoire that is biased towards bacterial and self-antigens, promoting a rapid response to infection and clearing of apoptotic cells. Although B-1a cells are known to primarily originate from fetal tissues, the mechanisms by which they arise has been a topic of debate for many years.
View Article and Find Full Text PDFNat Immunol
October 2019
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL, USA.
In B lymphopoiesis, activation of the pre-B cell antigen receptor (pre-BCR) is associated with both cell cycle exit and Igk recombination. Yet how the pre-BCR mediates these functions remains unclear. Here, we demonstrate that the pre-BCR initiates a feed-forward amplification loop mediated by the transcription factor interferon regulatory factor 4 and the chemokine receptor C-X-C motif chemokine receptor 4 (CXCR4).
View Article and Find Full Text PDFNat Immunol
April 2019
Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, USA.
Two-photon excitation microscopy (TPEM) has revolutionized the understanding of adaptive immunity. However, TPEM usually requires animal models and is not amenable to the study of human disease. The recognition of antigen by T cells requires cell contact and is associated with changes in T cell shape.
View Article and Find Full Text PDFNat Commun
September 2018
Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. Here we show that in small pre-B cells, the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding.
View Article and Find Full Text PDFFront Immunol
July 2018
Respiratory Medicine Unit, Department of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden.
Vimentin has been implicated in pulmonary sarcoidosis as a T-cell autoantigen, particularly in the context of , the Vα2.3/Vβ22 T-cell receptor (TCR), and Löfgren's syndrome. As vimentin is a known antigenic target in B-cell-mediated autoimmunity, we investigated humoral anti-vimentin responses in pulmonary sarcoidosis and their relationship with .
View Article and Find Full Text PDFSci Rep
July 2018
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The limited ability of current influenza virus vaccines to protect from antigenically drifted or shifted viruses creates a public health problem that has led to the need to develop effective, broadly protective vaccines. While current influenza virus vaccines mostly induce an immune response against the immunodominant and variable head domain of the hemagglutinin, the major surface glycoprotein of the virus, the hemagglutinin stalk domain has been identified to harbor neutralizing B-cell epitopes that are conserved among and even between influenza A virus subtypes. A complete understanding of the differences in evolution between the main target of current vaccines and this more conserved stalk region are missing.
View Article and Find Full Text PDFJ Autoimmun
June 2018
Gwen Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Chicago, IL, 60637, USA.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease accompanied by production of autoantibodies directed to a variety of self-proteins and nucleic acids. The genetic basis of SLE is also complex with at least 40 susceptibility loci identified. This complexity suggests that there are a variety of SLE manifestations; nevertheless, SLE is treated as a single disease clinically.
View Article and Find Full Text PDFNat Commun
November 2017
Committee on Immunology, University of Chicago, Chicago, IL, 60637, USA.
In the original PDF version of this Article, which was published on 16 October 2017, the publication date was incorrectly given as 11 October 2017. This has now been corrected in the PDF; the HTML version of the paper was correct from the time of publication.
View Article and Find Full Text PDFJ Exp Med
December 2017
Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, Departments of Medicine and Pathology, University of Chicago, Chicago, IL
A wealth of in vitro data has demonstrated a central role for receptor ubiquitination in endocytic sorting. However, how receptor ubiquitination functions in vivo is poorly understood. Herein, we report that ablation of B cell antigen receptor ubiquitination in vivo uncouples the receptor from CD19 phosphorylation and phosphatidylinositol 3-kinase (PI3K) signals.
View Article and Find Full Text PDFNat Commun
October 2017
Committee on Immunology, University of Chicago, Chicago, IL, 60637, USA.
Zbtb16-encoded PLZF is a signature transcription factor (TF) that directs the acquisition of T-helper effector programs during the development of multiple innate lymphocyte lineages, including natural killer T cell, innate lymphoid cell, mucosal-associated invariant T cell and γδ lineages. PLZF is also essential in osteoblast and spermatogonial development. How Zbtb16 itself is regulated in different lineages is incompletely understood.
View Article and Find Full Text PDFSci Immunol
January 2017
Committee on Immunology, University of Chicago, Chicago, IL 60615, USA.
In this study, we report that antigen-specific CD19CD27CD21 (CD21) B cells are transiently induced 14 to 28 days after immunization, at the time germinal centers (GCs) peak. Although clonally related to memory B cells and plasmablasts, CD21 cells form distinct clades within phylogenetic trees based on accumulated variable gene mutations, supporting exit from active GCs. CD21 cells express a transcriptional program, suggesting that they are primed for plasma cell differentiation and are refractory to GC differentiation, although they do not spontaneously secrete antibody.
View Article and Find Full Text PDFNat Med
December 2016
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for ∼60% of the response.
View Article and Find Full Text PDFJ Immunol Methods
November 2016
Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 924 E 57th Street R422, Chicago, IL 60637, USA; Committee on Immunology, University of Chicago, USA. Electronic address:
Generating monoclonal antibodies from single B cells is a valuable tool for characterizing the specificity and functional properties of humoral responses. We and others developed protocols that have facilitated major advances in our understanding of B cell development, tolerance, and effector responses to HIV and influenza. Here, we demonstrate various refinements and dramatically reduce the time required to produce recombinant antibodies.
View Article and Find Full Text PDFJ Clin Rheumatol
September 2016
From the *Pritzker School of Medicine, †Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, and ‡Section of Hematology and Oncology, University of Chicago, Chicago, IL.
Atypical hemolytic uremic syndrome is characterized by the presence of thrombocytopenia, microangiopathic hemolytic anemia, and end-organ injury. In this report, we describe two patients with systemic lupus erythematosus who presented with findings compatible with atypical hemolytic uremic syndrome, complicated by acute kidney injury that was refractory to conventional therapies. Both patients exhibited a response to eculizumab, a monoclonal antibody to complement protein C5, with stabilization of their platelet count.
View Article and Find Full Text PDFCurr Opin Rheumatol
September 2016
Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
Purpose Of Review: Despite recent developments and treatment successes, the outcome, and prognosis of patients with lupus nephritis (LuN) have not greatly changed since the 1980s. This review covers the application of new concepts to the understanding of renal inflammation and the study of new pharmacologic agents to improve patient outcomes.
Recent Findings: Studies have shown that the presence of anti-vimentin antibodies and T follicular helper cells in patient biopsies is associated with more severe interstitial inflammation, which has been tied to faster disease progression and onset of end-stage renal disease.
Nat Immunol
February 2016
Research Department, MedImmune, Gaithersburg, Maryland, USA.
Sci Transl Med
December 2015
Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA. Committee on Immunology, The University of Chicago, Chicago, IL 60637, USA.
Generating a broadly protective influenza vaccine is critical to global health. Understanding how immune memory influences influenza immunity is central to this goal. We undertook an in-depth study of the B cell response to the pandemic 2009 H1N1 vaccine over consecutive years.
View Article and Find Full Text PDFSemin Nephrol
September 2015
Department of Pathology, University of Chicago, Chicago, IL.
Nephritis is a common complication of systemic lupus erythematosus for which current therapies often prove inadequate. Current lupus nephritis classification systems emphasize glomerular acuity and scarring. However, tubulointerstitial inflammation (TII) and scarring are much better predictors of progression to renal failure.
View Article and Find Full Text PDFAnn Rheum Dis
October 2016
Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA.
Objective: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement.
Methods: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry.
Nat Immunol
October 2015
Department of Medicine, Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA.
B lymphopoiesis requires that immunoglobulin genes be accessible to RAG1-RAG2 recombinase. However, the RAG proteins bind widely to open chromatin, which suggests that additional mechanisms must restrict RAG-mediated DNA cleavage. Here we show that developmental downregulation of interleukin 7 (IL-7)-receptor signaling in small pre-B cells induced expression of the bromodomain-family member BRWD1, which was recruited to a specific epigenetic landscape at Igk dictated by pre-B cell receptor (pre-BCR)-dependent Erk activation.
View Article and Find Full Text PDFCell
August 2015
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, Box 208011, New Haven, CT 06520-8011, USA; Howard Hughes Medical Institute, 295 Congress Avenue, New Haven, CT 06511, USA. Electronic address:
The RAG1 endonuclease, together with its cofactor RAG2, is essential for V(D)J recombination but is a potent threat to genome stability. The sources of RAG1 mis-targeting and the mechanisms that have evolved to suppress it are poorly understood. Here, we report that RAG1 associates with chromatin at thousands of active promoters and enhancers in the genome of developing lymphocytes.
View Article and Find Full Text PDFComp Med
October 2014
Department of Biology, Ball State University, Muncie, Indiana, USA.
Oral tolerance is dependent on the complex architecture of the mucosal system of the gastrointestinal tract, its associated lymphoid tissue, and specialized immune cells. Changes in this architecture or the failure of any of its components may hinder the generation of oral tolerance. The larynx and esophagus are the gateway to the gastrointestinal tract, serving as the site of oral antigen introduction to the immune system and may have an important role in establishing tolerance.
View Article and Find Full Text PDFFront Immunol
June 2014
Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL , USA.
The essential events of B-cell development are the stochastic and sequential rearrangement of immunoglobulin heavy (Igμ) and then light chain (Igκ followed by Igλ) loci. The counterpoint to recombination is proliferation, which both maintains populations of pro-B cells undergoing Igμ recombination and expands the pool of pre-B cells expressing the Igμ protein available for subsequent Igκ recombination. Proliferation and recombination must be segregated into distinct and mutually exclusive developmental stages.
View Article and Find Full Text PDFSci Transl Med
April 2014
Section of Rheumatology, Department of Medicine and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
T follicular helper (TFH) cells are critical for B cell activation in germinal centers and are often observed in human inflamed tissue. However, it is difficult to know if they contribute in situ to inflammation. Expressed markers define TFH subsets associated with distinct functions in vitro.
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