A5020535485- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Sphingolipid Metabolism and Signaling
- Animal Genetics and Reproduction
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Viral Infectious Diseases and Gene Expression in Insects
- Immunodeficiency and Autoimmune Disorders
- HIV Research and Treatment
- Cell Adhesion Molecules Research
- Cancer Treatment and Pharmacology
- Protein purification and stability
- Diabetes and associated disorders
- Lung Cancer Treatments and Mutations
- NF-κB Signaling Pathways
- Molecular Biology Techniques and Applications
- Pneumonia and Respiratory Infections
- Glycosylation and Glycoproteins Research
- HER2/EGFR in Cancer Research
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
University of Colorado Denver
2016-2025
Tempus Labs (United States)
2024-2025
University of Colorado Anschutz Medical Campus
2016-2025
National Jewish Health
2013-2023
Centro de Investigación del Cáncer
2023
Cancer Research Center
2023
Lakeland Health
2022
Corewell Health Blodgett Hospital
2022
Spectrum Health
2022
University of Colorado Cancer Center
2021
Only mature B lymphocytes can enter the lymphoid follicles of spleen and lymph nodes thus efficiently participate in immune response. Mature, long-lived derive from short-lived precursors generated bone marrow. We show that selection into pool is an active process takes place spleen. Two populations splenic cells were identified as for cells. Transitional type 1 (T1) are recent immigrants They develop transitional 2 (T2), which cycling found exclusively primary Mature be T1 or T2
The immunoglobulin α (Ig-α)-Ig-β heterodimer is the signaling component of antigen receptor complex on B cells (BCR) and cell progenitors (pre-BCR). A mouse mutant that lacks most Ig-α cytoplasmic tail exhibits only a small impairment in early development but severe block generation peripheral pool, revealing checkpoint maturation ensures expression functional BCR mature cells. do develop demonstrate differential dependence antibody responses such signaling-competent appears to be critical...
Humoral immunity to viruses and encapsulated bacteria is comprised of T cell–independent type 2 (TI-2) antibody responses that are characterized by rapid production marginal zone B1 B cells. We demonstrate toll-like receptor (TLR) ligands influence the TI-2 response not only enhancing overall magnitude but also skewing this one dominated IgG isotypes. Importantly, TLR facilitate inducing I interferon (IFN), which in turn elicits significant amounts antigen-specific IgG2c predominantly from...
Roberta Pelanda and Raul M. Torres Integrated Department of Immunology, National Jewish Health University Colorado Denver School Medicine, Denver, 80206 Correspondence: pelandar{at}njhealth.org
Abstract The hematopoietic humanized mouse (hu-mouse) model is a powerful resource to study and manipulate the human immune system. However, major recurrent issue with this has been poor maturation of B cells that fail progress beyond transitional cell stage. Of interest, similar problem reported in transplant patients who receive cord blood stem cells. In study, we characterize development T lymph nodes (LNs) spleen BALB/c-Rag2nullIl2rγnull hu-mice. We find dominant population immature...
Abstract Lysophosphatidic acid (LPA) is a bioactive lipid which increases in concentration locally and systemically across different cancer types. Yet, the exact mechanism(s) of how LPA affects CD8 T cell immunosurveillance during tumor progression remain unknown. We show receptor (LPAR) signaling by cells promotes tolerogenic states via metabolic reprogramming potentiating exhaustive-like differentiation to modulate anti-tumor immunity. found levels predict response immunotherapy Lpar5...
The DNA-binding, fluorescent dye 7-amino-actinomycin D (7AAD) is efficiently excited by the 488 nm laser line commonly used in flow cytometry, but yields fluorescence emission further into red spectrum than alternative DNA-specific fluorochromes. In this report, we show that spectral properties of 7AAD allow single-laser analysis DNA content and cell cycle simultaneously with two surface markers labeled fluorescein (green)-and phycoerythrin (orange)-conjugated antibodies. use makes...
BAFF is an important prosurvival cytokine for mature B cells. However, previous studies have shown that BAFFR already expressed at the immature cell stage, and protein Bcl-2 does not completely complement defects resulting from absence of or BAFF. Thus, we hypothesized also functions to aid differentiation nonautoreactive cells into transitional promote their positive selection. We found higher levels on than autoreactive its expression correlates with surface IgM tonic BCR signaling. Our...
Renal transplant recipients who experience delayed graft function have increased risks of rejection and long-term failure. Ischemic damage is the most common cause function, although it known that tissue inflammation accompanies renal ischemia, unknown whether ischemia affects production antibodies by B lymphocytes, which may lead to chronic humoral allograft Here, mice immunized with a foreign antigen 24–96 hours after ischemia-reperfusion injury developed levels antigen-specific IgG1...
Abstract CD8 T lymphocytes are able to eliminate nascent tumor cells through a process referred as immunosurveillance. However, multiple inhibitory mechanisms within the microenvironment have been described that impede rejection by cells, including increased signaling receptors. Lysophosphatidic acid (LPA) is bioactive lysophospholipid has shown repeatedly promote diverse cellular processes benefiting tumorigenesis. Accordingly, exaggerated expression of LPA and receptors common feature cell...
Large intronic expansions of the triplet-repeat sequence (GAA.TTC) cause transcriptional repression Frataxin gene (FXN) leading to Friedreich's ataxia (FRDA). We previously found that GAA-triplet stimulate heterochromatinization in vivo transgenic mice. report here using chromosome conformation capture (3C) coupled with high-throughput sequencing GAA-repeat expansion FRDA cells stimulates a higher-order structure as fragment containing showed an increased interaction frequency genomic...
Chikungunya virus (CHIKV) and related alphaviruses cause epidemics of acute chronic musculoskeletal disease. To investigate the mechanisms underlying failure immune clearance CHIKV, we studied mice infected with an attenuated CHIKV strain (181/25) pathogenic parental (AF15561), which differ by five amino acids. Whereas AF15561 infection wild-type results in viral persistence joint tissues, 181/25 is cleared. In contrast, μMT lacking mature B cells suggesting that virus-specific antibody...
Persistent T cell antigen receptor (TCR) signaling by CD8 cells is a feature of cancer and chronic infections results in the sustained expression of, by, inhibitory receptors, which ultimately impair cytotoxic activity via poorly characterized mechanisms. We have previously determined that LPA5 GPCR expressed cells, upon engaging lysophosphatidic acid (LPA) bioactive serum lipid, functions as an able to negatively regulate TCR signaling. Notably, levels LPA autotaxin, phospholipase D enzyme...
The human B lymphocyte-specific Ag, CD22, is a cell adhesion molecule expressed on the surface during narrow window of development, coincident with IgD. A ligand for CD22 has recently been identified T cells as low molecular mass isoform leukocyte common CD45RO. reported to function in regulation both and activation vitro. In this study, we report isolation expression cDNA clone encoding murine homologue mCD22. Within their predicted protein sequences, sequences overall have 62% identity,...
Abstract Although IgM serves as a first barrier to Ag spreading, the cellular and molecular mechanisms following B lymphocyte activation that lead secretion are not fully understood. By virtue of their anatomical location, marginal zone (MZ) cells rapidly generate Ag-specific in response blood-borne pathogens play an important role protection against these potentially harmful Ags. In this study, we have explored contribution TLR agonists MZ cell mobilization well ability promote primary...
B cell receptors (BCRs) generate tonic signals critical for survival and early development. To determine whether these also mediate the development of transitional mature cells, we examined using a mouse strain in which nonautoreactive immunoglobulin heavy light chain–targeted cells express low surface BCR levels. We found that reduced expression translated into diminished strongly impaired cells. Constitutive Bcl-2 did not rescue differentiation BCR-low suggesting this defect was related to...