5,046 results
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2. Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein
- Author
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Han Li, Hai Jiang, Mingjun Sun, Qiongqiong Bai, Dehui Yin, Jingpeng Zhang, Xiling Wu, and Jihong Shao
- Subjects
Bacterial Diseases ,Serum Proteins ,B Cells ,RC955-962 ,Disease ,Pathology and Laboratory Medicine ,Biochemistry ,Epitope ,Cell Fusion ,Epitopes ,White Blood Cells ,Medical Conditions ,Filter Paper ,Animal Cells ,Zoonoses ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,biology ,Bacterial Pathogens ,Laboratory Equipment ,medicine.anatomical_structure ,Infectious Diseases ,Medical Microbiology ,Engineering and Technology ,Pathogens ,Cellular Types ,Public aspects of medicine ,RA1-1270 ,Bacterial Outer Membrane Proteins ,Research Article ,Neglected Tropical Diseases ,China ,Cell Physiology ,Immune Cells ,Immunology ,Equipment ,Enzyme-Linked Immunosorbent Assay ,Brucella ,Research and Analysis Methods ,Sensitivity and Specificity ,Microbiology ,Brucellosis ,Antigen ,Diagnostic Medicine ,medicine ,Humans ,Immunoassays ,Antibody-Producing Cells ,Microbial Pathogens ,B cell ,Antigens, Bacterial ,Blood Cells ,Bacteria ,business.industry ,Public Health, Environmental and Occupational Health ,Organisms ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,biology.organism_classification ,Tropical Diseases ,Fusion protein ,Virology ,Infectious disease (medical specialty) ,Immunologic Techniques ,business - Abstract
Background Brucellosis, as a serious zoonotic infectious disease, has been recognized as a re-emerging disease in the developing countries worldwide. In china, the incidence of brucellosis is increasing each year, seriously threatening the health of humans as well as animal populations. Despite a quite number of diagnostic methods currently being used for brucellosis, innovative technologies are still needed for its rapid and accurate diagnosis, especially in area where traditional diagnostic is unavailable. Methodology/Principal findings In this study, a total of 22 B cell linear epitopes were predicted from five Brucella outer membrane proteins (OMPs) using an immunoinformatic approach. These epitopes were then chemically synthesized, and with the method of indirect ELISA (iELISA), each of them displayed a certain degree of capability in identifying human brucellosis positive sera. Subsequently, a fusion protein consisting of the 22 predicted epitopes was prokaryotically expressed and used as diagnostic antigen in a newly established brucellosis testing method, nano-ZnO modified paper-based ELISA (nano-p-ELISA). According to the verifying test using a collection of sera collected from brucellosis and non-brucellosis patients, the sensitivity and specificity of multiepitope based nano-p-ELISA were 92.38% and 98.35% respectively. The positive predictive value was 98.26% and the negative predictive value was 91.67%. The multiepitope based fusion protein also displayed significantly higher specificity than Brucella lipopolysaccharide (LPS) antigen. Conclusions B cell epitopes are important candidates for serologically testing brucellosis. Multiepitope fusion protein based nano-p-ELISA displayed significantly sensitivity and specificity compared to Brucella LPS antigen. The strategy applied in this study will be helpful to develop rapid and accurate diagnostic method for brucellosis in human as well as animal populations., Author summary Brucellosis is one of the most important zoonosis in the world and has caused tremendous economic losses in agriculture and animal husbandry in many countries. Developing rapid, sensitive and specific diagnostic methods is very important for early detection and treatment of brucellosis patients. In this study, a novel diagnostic technique, nano-ZnO modified paper ELISA, was established. The antigen used in this technique was a fusion protein containing multiple B cell epitopes, which were predicted from Brucella major outer membrane proteins such as Bp26, Omp31, Omp16, Omp2b and Omp25. Comparing to traditional LPS antigen, this multiepitope based antigen displayed considerably higher sensitivity and higher specificity in laboratory. With the strategy described in this paper, more efficient epitopes and protein antigen can be identified in the future. Currently, LPS antigen is only prepared from live Brucella, while protein antigen can be produced in large quantities in prokaryotic expression system. In addition to nano-p-ELISA, this protein antigen can also be used for development other methods such as fluorescent polarization assay (FPA) and immunochromatographic assay (ICA) to meet the varied demand for brucellosis testing.
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- 2021
3. Correction: Suleman et al. Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation. Vaccines 2021, 9 , 1210
- Author
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Suleman, Muhammad, Tahir ul Qamar, Muhammad, Kiran, Rasool, Samreen, Rasool, Aneela, Albutti, Aqel, Alsowayeh, Noorah, Alwashmi, Ameen S. S., Aljasir, Mohammad Abdullah, Ahmad, Sajjad, Hussain, Zahid, Rizwan, Muhammad, Ali, Syed Shujait, Khan, Abbas, and Wei, Dong-Qing
- Subjects
TICK-borne encephalitis viruses ,B cells ,MOLECULAR docking ,DYNAMIC simulation ,IMMUNE response - Abstract
This correction notice addresses an error in a published paper titled "Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation." The authors discovered that the abstract of the paper was an exact duplicate of the abstract from a previously published paper by the same authors. This mistake occurred due to a wrong version being mistakenly uploaded during the publication process. The corrected abstract provides information about the design of a potential antigenic and non-allergenic multi-epitope subunit vaccine against TBEV, which shows promise for both in vitro and in vivo analyses. The authors state that this error does not affect the scientific conclusions of the paper. [Extracted from the article]
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- 2024
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4. Correction: Chakraborty et al. Bromelain a Potential Bioactive Compound: A Comprehensive Overview from a Pharmacological Perspective. Life 2021, 11 , 317.
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Chakraborty, Arka Jyoti, Mitra, Saikat, Tallei, Trina E., Tareq, Abu Montakim, Nainu, Firzan, Cicia, Donatella, Dhama, Kuldeep, Emran, Talha Bin, Simal-Gandara, Jesus, and Capasso, Raffaele
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BROMELIN ,B cells ,BIOACTIVE compounds ,OVALBUMINS ,BERBERINE ,REPERFUSION ,APIS cerana - Abstract
This document is a correction notice for a paper on the potential bioactive compound bromelain. The authors have identified errors in one section of the paper and provide revised references. The corrected table includes therapeutic studies of bromelain based on experimental studies. The document also includes a compilation of various scientific studies and articles related to the use of bromelain for various medical purposes. The studies explore the potential benefits of bromelain in treating conditions such as cancer, inflammation, thrombosis, and pain. The document provides a comprehensive overview of the scientific research on bromelain and its potential applications in medicine. [Extracted from the article]
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- 2024
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5. Enhanced mitochondrial function in B cells from elderly type-2 diabetes mellitus patients supports intrinsic inflammation.
- Author
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Frasca, Daniela and Bueno, Valquiria
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MITOCHONDRIAL physiology ,IN vitro studies ,FLOW cytometry ,PEARSON correlation (Statistics) ,RESEARCH funding ,BODY mass index ,ACADEMIC medical centers ,T-test (Statistics) ,INFLUENZA vaccines ,VACCINE effectiveness ,POLYMERASE chain reaction ,ENZYME-linked immunosorbent assay ,AGE distribution ,DESCRIPTIVE statistics ,HEMAGGLUTINATION tests ,METABOLITES ,MESSENGER RNA ,TYPE 2 diabetes ,AMYLOID ,STATISTICS ,INFLAMMATION ,CYTOKINES ,FACTOR analysis ,DATA analysis software ,B cells ,OBESITY ,C-reactive protein ,TUMOR necrosis factors ,INTERLEUKINS ,BIOMARKERS - Abstract
In this paper, we measured B cell function in elderly healthy individuals (E
H ) and in elderly patients with Type-2 Diabetes Mellitus (T2DM, ET2DM ), which are treatment-naive, as compared to healthy young (YH ) individuals. Results show a higher serum inflammatory status of elderly versus young individuals, and especially of ET2DM versus EH . This status is associated with a reduced response to the seasonal influenza vaccine and with increased frequencies of the circulating pro-inflammatory B cell subset called Double Negative (DN) B cells. B cells from ET2DM patients are not only more inflammatory but also hyper-metabolic as compared to those from EH controls. The results herein are to our knowledge the first to show that T2DM superimposed on aging further increases systemic and B cell intrinsic inflammation, as well as dysfunctional humoral immunity. Our findings confirm and extend our previously published findings showing that inflammatory B cells are metabolically supported. [ABSTRACT FROM AUTHOR]- Published
- 2024
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6. Dynamics of Activation and Regulation of the Immune Response to Attack by Viral Pathogens Using Mathematical Modeling.
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Cuesta-Herrera, Ledyz, Pastenes, Luis, Arencibia, Ariel D., Córdova-Lepe, Fernando, and Montoya, Cristhian
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REGULATORY T cells ,IMMUNOREGULATION ,CYTOTOXIC T cells ,B cells ,SARS-CoV-2 ,T cells ,HOMEOSTASIS - Abstract
In this paper, a mathematical model is developed to simulate the activation of regulatory T lymphocytes dynamics. The model considers the adaptive immune response and consists of epithelial cells, infected cells, free virus particles, helper and cytotoxic T lymphocytes, B lymphocytes, and regulatory T lymphocytes. A mathematical analysis was carried out to discuss the conditions of existence and stability of equilibrium solutions in terms of the basic reproductive number. In addition, the definitions and properties necessary to preserve the positivity and stability of the model are shown. The precision of these mathematical models can be affected by numerous sources of uncertainty, partly due to the balance between the complexity of the model and its predictive capacity to depict the biological process accurately. Nevertheless, these models can provide remarkably perspectives on the dynamics of infection and assist in identification specific immunological traits that improve our comprehension of immune mechanisms. The theoretical results are validated by numerical simulations using data reported in the literature. The construction, analysis, and simulation of the developed models demonstrate that the increased induced regulatory T lymphocytes effectively suppress the inflammatory response in contrast to similar cells at lower contents, playing a key role in maintaining self-tolerance and immune homeostasis. [ABSTRACT FROM AUTHOR]
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- 2024
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7. The challenges and breakthroughs in the development of diagnostic monoclonal antibodies.
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Wang, Jing, Song, Qitao, Yang, Tao, Li, Yuanli, Zhang, Lihua, Li, Jiayan, Liu, Feifei, Lin, Yanyin, Xu, Xiaoxia, Heng, Yu, Xu, Lulai, Zhang, Shun, Zhou, Jiahui, Liu, Yunbo, Kong, Lingyuan, Tang, Dingbin, Ji, Chengdong, Tan, Bing, Liao, Pu, and Pan, Nengke
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MONOCLONAL antibodies ,B cells ,ARTIFICIAL intelligence ,SYNTHETIC antibodies ,ANTIBODY formation ,TECHNOLOGICAL innovations ,DISPLAY systems ,MACHINE learning - Abstract
Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Peritumoral B cells drive proangiogenic responses in HMGB1-enriched esophageal squamous cell carcinoma
- Author
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Ying Wang, Reshma Shakya, Anthony Wing Ip Lo, Rajiv Khanna, Ka Chun Wu, Xin Yuan Guan, Leo Y. C. Yan, Dora L.W. Kwong, Yanru Qin, Wei Dai, Simon Law, Ngar-Woon Kam, and Victor Ho-Fun Lee
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Cancer Research ,Esophageal Neoplasms ,Physiology ,Angiogenesis ,medicine.medical_treatment ,Clinical Biochemistry ,chemical and pharmacologic phenomena ,HMGB1 ,Umbilical vein ,Transcriptome ,Mice ,High-mobility group box 1 ,Esophageal squamous cell carcinoma ,Cell Line, Tumor ,medicine ,Human Umbilical Vein Endothelial Cells ,Tumor Microenvironment ,Animals ,Humans ,HMGB1 Protein ,Cell Proliferation ,Tube formation ,Tumor microenvironment ,Original Paper ,B cells ,biology ,Neovascularization, Pathologic ,Chemistry ,Glycyrrhizic Acid ,Gene Expression Regulation, Neoplastic ,Cytokine ,Cell culture ,Cancer research ,biology.protein - Abstract
Several B-cell subsets with distinct functions and polarized cytokine profiles that extend beyond antibody production have been reported in different cancers. Here we have demonstrated that proliferating B cells were predominantly found in the peritumoral region of esophageal squamous cell carcinoma (ESCC). These B cells were enriched in tumor nests with high expression of high-mobility group box 1 (HMGB1). High densities of peritumoral proliferating B cells and concomitantly high intratumoral HMGB1 expression showed improved prognostic significance, surpassing prognostic stratification of ESCC patients based on HMGB1 positivity alone. This striking association led us to set up models to test whether cancer-derived HMGB1 could shape tumor microenvironment via modulation on B cells. Overexpression of HMGB1 in ESCC cell lines (KYSE510 and EC18) enhanced proliferation and migration of B cells. Transcriptomic analysis showed that migratory B cells exhibited high enrichment of proangiogenic genes. VEGF expression in proliferating B cells was induced upon co-culture of HMGB1-overexpressing tumor cells and B cells. Secretome array profiling of conditioned media (CM) from the co-culture revealed rich expression of proangiogenic proteins. Consequently, incubation of human umbilical vein endothelial cells with CM promoted angiogenesis in tube formation and migration assays. HMGB1 inhibitor, glycyrrhizin, abolishes all the observed proangiogenic phenotypes. Finally, co-injection of B cells and CM with HMGB1-overexpressing tumor cells, but not with glycyrrhizin, significantly enhanced tumor growth associated with increased microvascular density in ESCC xenograft mice model. Our results indicate that cancer-derived HMGB1 elevates angiogenesis in ESCC by shifting the balance toward proangiogenic signals in proliferating B cells. Supplementary Information The online version contains supplementary material available at 10.1007/s10456-021-09819-0.
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- 2021
9. Licochalcone A improves the cognitive ability of mice by regulating T- and B-cell proliferation
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Yating Wu, Haifeng Liu, Jianbo Zhu, and Hailiang Liu
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Aging ,Licochalcone A ,T-Lymphocytes ,T cells ,Morris water navigation task ,Spleen ,Pharmacology ,Flow cytometry ,chemistry.chemical_compound ,Mice ,Immune system ,Chalcones ,Cognition ,cognitive ability ,medicine ,Animals ,Maze Learning ,Whole blood ,Cell Proliferation ,B cells ,B-Lymphocytes ,medicine.diagnostic_test ,licochalcone A ,Interleukin-17 ,Interleukin ,Cell Biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,chemistry ,Cerebral blood flow ,Research Paper - Abstract
Licochalcone A (LA), a flavonoid found in licorice, has anticancer, antioxidant, anti-inflammatory, and neuroprotective properties. Here, we explored the effect of injecting LA into the tail vein of middle-aged C57BL/6 mice on their cognitive ability as measured by the Morris water maze (MWM) test and cerebral blood flow (CBF). The related mechanisms were assessed via RNA-seq, and T (CD3e+) and B (CD45R/B220+) cells in the spleen and whole blood were quantified via flow cytometry. LA improved the cognitive ability, according to the MWM test results, and upregulated the CBF level of treated mice. The RNA-seq results indicate that LA affected the interleukin (IL)-17 signaling pathway, which is related to T- and B-cell proliferation, and the flow cytometry data suggest that LA promoted T- and B-cell proliferation in the spleen and whole blood. We also performed immune reconstruction via a tail vein injection of lymphocytes into B-NDG (NOD-PrkdcscidIl2rgtm1/Bcge) mice before treating them with LA. We tested cognitive ability by subjecting these animals to new object recognition tests and quantified the splenic and whole blood T and B cells. Cognitive ability improved after immune reconstruction and LA treatment, and LA promoted T- and B-cell proliferation in the spleen and whole blood. This study demonstrates that LA, by activating the IL-17 signaling pathway, promotes T- and B-cell proliferation in the spleen and whole blood of mice and improves cognitive ability. Thus, LA may have immune-modulating therapeutic potential for improving cognition.
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- 2021
10. Anti-Idiotypic mRNA Vaccine to Treat Autoimmune Disorders.
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Niazi, Sarfaraz K.
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AUTOIMMUNE diseases ,MESSENGER RNA ,AUTOANTIBODIES ,B cells ,T cells - Abstract
The 80+ existing autoimmune disorders (ADs) affect billions with little prevention or treatment options, except for temporary symptomatic management, leading to enormous human suffering and a monumental financial burden. The autoantibodies formed in most ADs have been identified, allowing the development of novel anti-idiotypic antibodies to mute the autoantibodies using vaccines. Nucleoside vaccines have been successfully tested as antigen-specific immunotherapies (ASI), with mRNA technology offering multi-epitope targeting to mute multiple autoantibodies. This paper proposes using mRNA technology to produce anti-idiotypic antibodies with broad effectiveness in preventing and treating them. This paper delves into the state-of-the-art mRNA design strategies used to develop novel ASIs by selecting appropriate T cell and B cell epitopes to generate anti-idiotypic antibodies. The low cost and fast development of mRNA vaccines make this technology the most affordable for the global control of ADs. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Lupus nephritis: clinical presentations and outcomes in the 21st century
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Gabriella Moroni, Andrea Doria, Michela Gasparotto, Mariele Gatto, and Valentina Binda
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medicine.medical_specialty ,030232 urology & nephrology ,Lupus nephritis ,B cells ,calcineurin inhibitors ,classification ,lupus nephritis ,prognosis ,renal biopsy ,risk factors ,Unmet needs ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Recurrence ,Epidemiology ,medicine ,Humans ,Pharmacology (medical) ,Intensive care medicine ,AcademicSubjects/MED00360 ,Disease prognosis ,030203 arthritis & rheumatology ,business.industry ,Mortality rate ,Remission Induction ,Retrospective cohort study ,medicine.disease ,Precision medicine ,Supplement Papers ,Disease Progression ,business - Abstract
Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.
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- 2020
12. B cells do not play a role in vaccine-mediated immunity against Marek’s disease
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Mohammad Heidari, Huanmin Zhang, Cari Hearn, and Lakshmi Sunkara
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Marek’s disease ,B cells ,Infectious Diseases ,General Veterinary ,General Immunology and Microbiology ,Regular paper ,Bursectomy ,Vaccination ,Public Health, Environmental and Occupational Health ,Molecular Medicine ,Immunologic diseases. Allergy ,RC581-607 ,Marek’s disease virus - Abstract
Background: Marek’s disease virus (MDV), a highly oncogenic α-herpesvirus, is the etiological agent of Marek’s disease (MD) in chickens. The antiviral activity of vaccine-induced immunity against MD reduces the level of early cytolytic infection, production of cell-free virions in the feather follicle epithelial cells (FFE), and lymphoma formation. Despite the success of several vaccines that have greatly reduced the economic losses from MD, the mechanism of vaccine-induced immunity is poorly understood. Methods: To provide insight into possible role of B cells in vaccine-mediated protection, we bursectomized birds on day of hatch and vaccinated them eight days later. The birds were challenged 10 days post vaccination with or without receiving adoptive lymphocytes from age-matched control birds prior to inoculation. The study also included vaccinated/challenged and non-vaccinated challenged intact birds. Flowcytometric analysis of PBMN cells were conducted twice post bursectomy to confirm B cell depletion and assess the effect of surgery on T cell population. Immunohistochemical analysis and viral genome copy number assessment in the skin samples at termination was performed to measure the replication rate of MDV in the FFE of the skin tissues of the challenged birds. Results: The non-vaccinated/challenged birds developed typical clinical signs of MD while the vaccinated/challenged and bursectomized, vaccinated/challenged groups with or without adoptive lymphocyte transfer, were fully protected with no sign of transient paralysis, weight loss, or T cell lymphomas. Immunohistochemical analysis and viral genome copy number evaluation in the skin samples revealed that unlike the vaccinated/challenged birds a significant number of virus particles were produced in the FFE of the non-vaccinated/challenged birds at termination. In the bursectomized, vaccinated/challenged groups, only a few replicating virions were detected in the skin of birds that received adoptive lymphocytes prior to challenge. Conclusions: The study shows that B cells do not play a critical role in MD vaccine-mediated immunity.
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- 2022
13. Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity
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Mark Cascione, Chongshu Chen, Tomasz Zielinski, Catherine Miller, Becky Parks, David Brassat, Shivani Kapadia, Yang Mao-Draayer, Diana Xing, Derrick Robertson, Erin E. Longbrake, Eris Bame, and Jason P. Mendoza
- Subjects
lymphocytes ,medicine.drug_class ,Dimethyl Fumarate ,Cell ,Anti-Inflammatory Agents ,multiple sclerosis ,Anti-inflammatory ,03 medical and health sciences ,chemistry.chemical_compound ,Multiple Sclerosis, Relapsing-Remitting ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Prospective Studies ,Delayed-release dimethyl fumarate ,030304 developmental biology ,B cells ,0303 health sciences ,Dimethyl fumarate ,biology ,Multiple sclerosis ,Absolute lymphocyte count ,medicine.disease ,Immunity, Humoral ,medicine.anatomical_structure ,Neurology ,chemistry ,Immunology ,Humoral immunity ,biology.protein ,Neurology (clinical) ,Neoplasm Recurrence, Local ,Antibody ,Original Research Papers ,immunoglobulin ,Immunosuppressive Agents ,030217 neurology & neurosurgery - Abstract
Background: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment. Objective: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment. Methods: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc). Results: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL–W96), stabilizing above the lower limit of normal (baseline: 1.82 × 109/L; W48: 1.06 × 109/L; W96: 1.05 × 109/L). CD4 + and CD8 + T cells correlated highly with ALC from BL–W96 ( p + and CD8 + T cells increased, whereas CD4 + and CD8 + central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1–4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs. Conclusion: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia. Support: Biogen
- Published
- 2020
14. Interleukin 39: a new member of interleukin 12 family
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Keye Xu, Xiaoying Wang, Zhiyu Lu, Mingcai Li, and Yan Li
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Review Paper ,B cells ,biology ,Chemistry ,Immunology ,Interleukin ,Inflammation ,EBI3 ,Glycoprotein 130 ,Molecular biology ,acute coronary syndrome ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,medicine ,Interleukin 12 ,STAT protein ,biology.protein ,Immunology and Allergy ,interleukin 12 ,medicine.symptom ,Receptor ,STAT3 ,interleukin 39 ,030215 immunology - Abstract
Interleukin (IL)-12 family member is a heterodimer glycoprotein, composed of two covalently linked subunits, α and β chains. The α subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the β subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-39 is a new heterodimeric IL-12 family member composed of IL-23p19 and Ebi3 subunits. IL-39 is secreted by lipopolysaccharide-stimulated B cells. Other immune cells, such as dendritic cells and macrophages, express IL-39 mRNA. In lupus-like mice, GL7+B cells and CD138+plasma cells are highly activated and widely expressed, promoting high expression of IL-39. IL-39 mediates inflammatory responses through binding to a heterodimer of IL-23R/gp130 receptor and activation of signal transducer and activator of transcription (STAT)1/STAT3 signal molecules. The serum levels of IL-39 were significantly increased in patients with acute coronary syndrome compared with patients with normal coronary arteries. This review discusses the biological characteristics, receptor, and signal pathway as well as biological activity of IL-39 and its potential role in inflammation and other diseases.
- Published
- 2020
15. Method for B Cell Receptor Enrichment in Malignant B Cells.
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Bhattacharyya, Puja, Christopherson, Richard I., Skarratt, Kristen K., and Fuller, Stephen J.
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PROTEIN analysis ,RESEARCH funding ,IMMUNE system ,ANTIGENS ,MASS spectrometry ,PROTEOMICS ,B cells - Abstract
Simple Summary: The B cell receptor (BCR) is a membrane-bound protein complex that is required for the normal development of B cells. BCR signalling is also involved in the pathogenesis of B cell cancers. While there is substantial literature on genomic analyses of the BCR, there are limited proteomic studies of receptor structure and its interactions with neighbouring proteins. This is partly due to the location of the BCR in the surface-membrane lipid environment that has limited the ability to enrich the complex for proteomic analysis. Here, we report an enrichment technique that can be used for mass spectrometry analyses of the BCR from live B cells. B cells are central to the adaptive immune response and provide long-lasting immunity after infection. B cell activation is mediated by the surface membrane-bound B cell receptor (BCR) following recognition of a specific antigen. The BCR has been challenging to analyse using mass spectrometry (MS) due to the difficulty of isolating and enriching this membrane-bound protein complex. There are approximately 120,000 BCRs on the B cell surface; however, depending on the B cell activation state, there may be hundreds-of-millions to billions of proteins in a B cell. Consequently, advanced proteomic techniques such as MS workflows that use purified proteins to yield structural and protein-interaction information have not been published for the BCR complex. This paper describes a method for enriching the BCR complex that is MS-compatible. The method involves a Protein G pull down on agarose beads using an intermediary antibody to each of the BCR complex subcomponents (CD79a, CD79b, and membrane immunoglobulin). The enrichment process is shown to pull down the entire BCR complex and has the advantage of being readily compatible with further proteomic study including MS analysis. Using intermediary antibodies has the potential to enrich all isotypes of the BCR, unlike previous methods described in the literature that use protein G-coated beads to directly pull down the membrane IgG (mIgG) but cannot be used for other mIg isotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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16. EXPERIMENTAL PLAN BASED ON THE RANDOMIZED COMPLETE BLOCK METHOD FOR THE DEVELOPMENT OF FLEXIBLE MATERIALS FOR ELECTROMAGNETIC ATTENUATION.
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Raluca Maria, AILENI, Cornel Adrian, MARIN, and Laurentiu Cristian, DINCA
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ELECTROMAGNETIC waves ,ELECTROMAGNETIC shielding ,KILLER cells ,ELECTROMAGNETIC devices ,B cells - Abstract
The negative effects of continuous exposure to electromagnetic waves know a continuous growth on the last years because of new developments in electronics and mobile communication applications in different fields (medical, smart devices for IoT applications). There are some researches concluding that exposure to electromagnetic fields could affect the cells (PMBCs, T lymphocytes, B lymphocytes, NK cells and macrophages) of the immune system including cell proportion, cell cycle, apoptosis, destruction activity and cytokine content. Considering the negative effect of electromagnetic inference, it is necessary to develop advanced materials to attenuate electromagnetic waves to protect electronic equipment and humans. In this context, this paper presents an experimental plan based on completely randomized blocks (RCBD) for obtaining adequate textile coating for electromagnetic shielding applications taking into account the design of electromagnetic shielding devices should include the modelling of the attenuation phenomenon of electromagnetic waves using Schelkunoff and Calculation theories. The proposed experimental plan consists of experiments distributed in blocks, each block corresponding to the technology used. For each experimental block, the factors specific to the technology used (independent variables such as the metals used (Ni, Cu, graphite, Fe3O4, Ag, Zn), mass (M), air permeability (Pa), thickness (d)) that could influence the response variable (electrical resistance (Rs)) have been taken into consideration. [ABSTRACT FROM AUTHOR]
- Published
- 2024
17. The Lung in Rheumatoid Arthritis—Friend or Enemy?
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Anton, Maria-Luciana, Cardoneanu, Anca, Burlui, Alexandra Maria, Mihai, Ioana Ruxandra, Richter, Patricia, Bratoiu, Ioana, Macovei, Luana Andreea, and Rezus, Elena
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LUNGS ,RHEUMATOID arthritis ,CHEMOKINE receptors ,INTERSTITIAL lung diseases ,SYNOVIAL membranes ,B cells ,IMMUNE system - Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune condition frequently found in rheumatological patients that sometimes raises diagnosis and management problems. The pathogenesis of the disease is complex and involves the activation of many cells and intracellular signaling pathways, ultimately leading to the activation of the innate and acquired immune system and producing extensive tissue damage. Along with joint involvement, RA can have numerous extra-articular manifestations (EAMs), among which lung damage, especially interstitial lung disease (ILD), negatively influences the evolution and survival of these patients. Although there are more and more RA-ILD cases, the pathogenesis is incompletely understood. In terms of genetic predisposition, external environmental factors act and subsequently determine the activation of immune system cells such as macrophages, neutrophils, B and T lymphocytes, fibroblasts, and dendritic cells. These, in turn, show the ability to secrete molecules with a proinflammatory role (cytokines, chemokines, growth factors) that will produce important visceral injuries, including pulmonary changes. Currently, there is new evidence that supports the initiation of the systemic immune response at the level of pulmonary mucosa where the citrullination process occurs, whereby the autoantibodies subsequently migrate from the lung to the synovial membrane. The aim of this paper is to provide current data regarding the pathogenesis of RA-associated ILD, starting from environmental triggers and reaching the cellular, humoral, and molecular changes involved in the onset of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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18. The Functional Mechanism of BP9 in Promoting B Cell Differentiation and Inducing Antigen Presentation.
- Author
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Hu, Jianing, Zhang, Ze, Cai, Jiaxi, Hao, Shanshan, Li, Chenfei, and Feng, Xiuli
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B cell differentiation ,ANTIGEN presentation ,PLASMA cells ,B cells ,CELL differentiation - Abstract
The Bursa of Fabricius, an avian unique humoral immune organ, is instrumental to B cell development. Bursal-derived peptide BP9 fosters B-cell development and formation. Yet, the exact mechanism wherein BP9 impacts B cell differentiation and antigenic presentation remains undefined. In this paper, B cell activation and differentiation in the spleen cells from mice immunized with the AIV vaccine and BP9 were detected following flow cytometry (FCM) analysis. Furthermore, the molecular mechanism of BP9 in B cell differentiation in vivo was investigated with RNA sequencing technology. To verify the potential functional mechanism of BP9 in the antigenic presentation process, the transcriptome molecular basis of chicken macrophages stimulated by BP9 was measured via high-throughput sequencing technology. The results proved that when given in experimental dosages, BP9 notably accelerated total B cells, and enhanced B-cell differentiation and plasma cell production. The gene expression profiles of B cells from mice immunized with 0.01 mg/mL BP9 and AIV vaccine disclosed that 0.01 mg/mL BP9 initiated the enrichment of several biological functions and significantly stimulated key B-cell pathways in immunized mice. Crucially, a total of 4093 differentially expressed genes were identified in B cells with BP9 stimulation, including 943 upregulated genes and 3150 downregulated genes. Additionally, BP9 induced various cytokine productions in the chicken macrophage HD11 cells and activated 9 upregulated and 20 downregulated differential miRNAs, which were involved in various signal and biological processes. Furthermore, BP9 stimulated the activation of multiple transcription factors in HD11 cells, which was related to antigen presentation processes. In summary, these results suggested that BP9 might promote B cell differentiation and induce antigen presentation, which might provide the valuable insights into the mechanism of B cell differentiation upon bursal-derived immunomodulating peptide stimulation and provide a solid experimental groundwork for enhancing vaccine-induced immunity. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Cadmium Exposure: Mechanisms and Pathways of Toxicity and Implications for Human Health.
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Qu, Fei and Zheng, Weiwei
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MITOGEN-activated protein kinases ,CADMIUM ,EPIGENOMICS ,POISONS ,CELL anatomy ,CELL communication ,B cells ,HISTONES - Abstract
Cadmium (Cd), a prevalent environmental contaminant, exerts widespread toxic effects on human health through various biochemical and molecular mechanisms. This review encapsulates the primary pathways through which Cd inflicts damage, including oxidative stress induction, disruption of Ca
2+ signaling, interference with cellular signaling pathways, and epigenetic modifications. By detailing the absorption, distribution, metabolism, and excretion (ADME) of Cd, alongside its interactions with cellular components such as mitochondria and DNA, this paper highlights the extensive damage caused by Cd2+ at the cellular and tissue levels. The role of Cd in inducing oxidative stress—a pivotal mechanism behind its toxicity—is discussed with emphasis on how it disrupts the balance between oxidants and antioxidants, leading to cellular damage and apoptosis. Additionally, the review covers Cd's impact on signaling pathways like Mitogen-Activated Protein Kinase (MAPK), Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor Protein 53 (p53) pathways, illustrating how its interference with these pathways contributes to pathological conditions and carcinogenesis. The epigenetic effects of Cd, including DNA methylation and histone modifications, are also explored to explain its long-term impact on gene expression and disease manifestation. This comprehensive analysis not only elucidates the mechanisms of Cd toxicity but also underscores the critical need for enhanced strategies to mitigate its public health implications. [ABSTRACT FROM AUTHOR]- Published
- 2024
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20. Unravelling B cell heterogeneity: insights into flow cytometrygated B cells from single-cell multi-omics data.
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Pernes, Jane I., Alsayah, Atheer, Tucci, Felicia, and Bashford-Rogers, Rachael J. M.
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B cells ,MULTIOMICS ,CELL populations ,CELL physiology ,HETEROGENEITY - Abstract
Introduction: B cells play a pivotal role in adaptive immunity which has been extensively characterised primarily via flow cytometry-based gating strategies. This study addresses the discrepancies between flow cytometry-defined B cell subsets and their high-confidence molecular signatures using single-cell multiomics approaches. Methods: By analysing multi-omics single-cell data from healthy individuals and patients across diseases, we characterised the level and nature of cellular contamination within standard flow cytometric-based gating, resolved some of the ambiguities in the literature surrounding unconventional B cell subsets, and demonstrated the variable effects of flow cytometric-based gating cellular heterogeneity across diseases. Results: We showed that flow cytometric-defined B cell populations are heterogenous, and the composition varies significantly between disease states thus affecting the implications of functional studies performed on these populations. Importantly, this paper draws caution on findings about B cell selection and function of flow cytometric-sorted populations, and their roles in disease. As a solution, we developed a simple tool to identify additional markers that can be used to increase the purity of flow-cytometric gated immune cell populations based on multi-omics data (AlliGateR). Here, we demonstrate that additional non-linear CD20, CD21 and CD24 gating can increase the purity of both naïve and memory populations. Discussion: These findings underscore the need to reconsider B cell subset definitions within the literature and propose leveraging single-cell multi-omics data for refined characterisation. We show that single-cell multi-omics technologies represent a powerful tool to bridge the gap between surface marker-based annotations and the intricate molecular characteristics of B cell subsets. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Genomic, transcriptomic and epigenomic sequencing data of the B-cell leukemia cell line REH.
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Lysenkova Wiklander, Mariya, Övernäs, Elin, Lagensjö, Johanna, Raine, Amanda, Petri, Anna, Wiman, Ann-Christin, Ramsell, Jon, Marincevic-Zuniga, Yanara, Gezelius, Henrik, Martin, Tom, Bunikis, Ignas, Ekberg, Sara, Erlandsson, Rikard, Larsson, Pontus, Mosbech, Mai-Britt, Häggqvist, Susana, Hellstedt Kerje, Susanne, Feuk, Lars, Ameur, Adam, and Liljedahl, Ulrika
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B cells ,WHOLE genome sequencing ,TRANSCRIPTOMES ,RNA sequencing ,LYMPHOBLASTIC leukemia ,LEUKEMIA - Abstract
Objectives: The aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development. Data description: This paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Compromised steady‐state germinal center activity with age in nonhuman primates
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Francois Villinger, Tirupataiah Sirupangi, Rajendra Pahwa, Lucio Gama, Kimberly Shankwitz, Kyle Blaine Russel, Constantinos Petrovas, Suresh Pallikkuth, Savita Pahwa, Richard A. Koup, Daniel Kvistad, and Li Pan
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,Aging ,medicine.medical_specialty ,Cell ,CD8-Positive T-Lymphocytes ,Biology ,Positive correlation ,Monocytes ,law.invention ,03 medical and health sciences ,follicles ,0302 clinical medicine ,Immune system ,Antigens, CD ,law ,Internal medicine ,Follicular phase ,medicine ,Animals ,Cytotoxic T cell ,Inflammation ,B-Lymphocytes ,Original Paper ,B cells ,Germinal center ,Forkhead Transcription Factors ,Cell Biology ,Germinal Center ,Macaca mulatta ,Lymphocyte Activation Gene 3 Protein ,Original Papers ,Immunity, Humoral ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Suppressor ,Lymph Nodes ,Steady state (chemistry) ,Tfh cells ,030217 neurology & neurosurgery ,Granulocytes - Abstract
Age‐related reductions in vaccine‐induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1hi CD4 T (Tfh) and proliferating (Ki67hi) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3hiLag3hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals. Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging. Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging., Steady‐state germinal center immune reactivity is compromised in aged NHPs. This loss of reactivity is characterized by changes in many GC associated cell populations including Tfh, B cells, and follicular Tregs.
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- 2019
23. Regulation of B cell functions by S-nitrosoglutathione in the EAE model
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Fei Qiao, Avtar K. Singh, Mushfiquddin Khan, Judong Kim, Inderjit Singh, S.M. Touhidul Islam, and Je-Seong Won
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0301 basic medicine ,Adoptive cell transfer ,Medicine (General) ,Encephalomyelitis, Autoimmune, Experimental ,QH301-705.5 ,Regulatory B cells ,medicine.medical_treatment ,T cell ,GSNO ,Clinical Biochemistry ,S-Nitrosoglutathione-reductase ,Biology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,R5-920 ,medicine ,Animals ,Biology (General) ,B cell ,GSNOR ,B cells ,IL-6 ,B-Lymphocytes ,Experimental autoimmune encephalomyelitis ,EAE ,Organic Chemistry ,medicine.disease ,Mice, Inbred C57BL ,Interleukin 10 ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Immunology ,IL-10 ,S-Nitrosoglutathione ,Cytokines ,030217 neurology & neurosurgery ,Research Paper - Abstract
B cells play both protective and pathogenic roles in T cell-mediated autoimmune diseases by releasing regulatory vs. pathogenic cytokines. B cell-depleting therapy has been attempted in various autoimmune diseases but its efficacy varies and can even worsen symptoms due to depletion of B cells releasing regulatory cytokines along with B cells releasing pathogenic cytokines. Here, we report that S-nitrosoglutathione (GSNO) and GSNO-reductase (GSNOR) inhibitor N6022 drive upregulation of regulatory cytokine (IL-10) and downregulation of pathogenic effector cytokine (IL-6) in B cells and protected against the neuroinflammatory disease of experimental autoimmune encephalomyelitis (EAE). In human and mouse B cells, the GSNO/N6022-mediated regulation of IL-10 vs. IL-6 was not limited to regulatory B cells but also to a broad range of B cell subsets and antibody-secreting cells. Adoptive transfer of B cells from N6022 treated EAE mice or EAE mice deficient in the GSNOR gene also regulated T cell balance (Treg > Th17) and reduced clinical disease in the recipient EAE mice. The data presented here provide evidence of the role of GSNO in shifting B cell immune balance (IL-10 > IL-6) and the preclinical relevance of N6022, a first-in-class drug targeting GSNOR with proven human safety, as therapeutics for autoimmune disorders including multiple sclerosis., Graphical abstract Image 1, Highlights • GSNO and GSNOR inhibitor (N6022) upregulates IL-10 and downregulates IL-6 in B cells. • GSNO/N6022-mediated cytokine regulation occurs in a broad range of B cell subsets. • GSNO/N6022 treatment ameliorates autoimmune disease of EAE. • B cell transfer from N6022-treated or GSNOR null EAE mice to EAE mice shifts T cell balance (Treg > Th17) and alleviates EAE. • The data provide the first insight into the therapeutic potential of GSNO/N6022 targeting B cells in multiple sclerosis.
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- 2021
24. Inhibition of B cell activation following
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Seung Y, Chu, Erik, Pong, Christine, Bonzon, Ning, Yu, Chaim O, Jacob, Samantha A, Chalmers, Chaim, Putterman, David E, Szymkowski, and William, Stohl
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FcγRIIb ,B cells ,Research paper ,Lupus ,Murine - Abstract
Engagement of Fcγ receptor IIb (FcγRIIb) suppresses B cell activation and represents a promising target for therapy in autoimmunity. Obexelimab is a non-depleting anti-human CD19 mAb with an Fc region engineered to have high affinity for human FcγRIIb, thereby co-engaging BCR and FcγRIIb. To assess its ability to suppress B cell activation in vivo, we generated non-autoimmune-prone C57BL/6 (B6) and SLE-prone NZM 2328 (NZM) mice in which the human FcγRIIb extracellular domain was knocked into the mouse Fcgr2b locus (B6.hRIIb and NZM.hRIIb mice, respectively, the latter retaining features of SLE). XENP8206, a mAb which bears the same FcγRIIb-enhanced human Fc domain as does obexelimab but which recognizes murine CD19 rather than human CD19, inhibited in vitro BCR-triggered activation of B cells from both B6.hRIIb and NZM.hRIIb mice. Following administration of XENP8206 to B6.hRIIb or NZM.hRIIb mice, B cell numbers in the spleen and lymph nodes remained stable but became hyporesponsive to BCR-triggered activation for at least 14 days. These findings demonstrate proof-of-principle that pharmacologic co-engagement of BCR and human FcγRIIb inhibits B cell activation in non-autoimmune and SLE-prone hosts while preserving B cell numbers. These observations lay a strong foundation for clinical trials in human SLE with agents that co-engage BCR and FcγRIIb. Moreover, B6.hRIIb and NZM.hRIIb should serve as powerful in vivo models in the elucidation of the cellular and molecular underpinnings of the changes induced by BCR/FcγRIIb co-engagement., Highlights • We generated non-autoimmune B6.hRIIb and SLE-prone NZM.hRIIb knockin mice for the human FcγRIIb extracellular domain. • XENP8206 is an anti-murine CD19 mAb engineered to have high affinity for human FcγRIIb. • XENP8206 inhibited in vitro BCR-triggered activation of B cells from both B6.hRIIb and NZM.hRIIb mice. • XENP8206 inhibited in vivo BCR-triggered activation of B cells while preserving B cell numbers. • These observations lay a strong foundation for clinical trials in human SLE with agents that co-engage BCR and FcγRIIb.
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- 2020
25. Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution.
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Pastor, Rocío, Puyssegur, Juliana, de la Guardia, M. Paula, Varón, Lindybeth Sarmiento, Beccaglia, Gladys, Spada, Nicolás, de Lima, Andrea Paes, Collado, M. Soledad, Blanco, Andrés, Scetti, Isabel Aspe, Arabolaza, M. Elena, Paoli, Bibiana, Chirdo, Fernando, and Arana, Eloísa
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B cells ,GERMINAL centers ,IMMUNOLOGIC memory ,T helper cells ,MUCOUS membranes - Abstract
Background: The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. Results: We found an age-dependent reduction in the proportion of germinal center B cell population (B
GC ) and its T cell counterpart (T follicular helper germinal center cells, TfhGC ). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+ CD39high CD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. Conclusions: This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites. [ABSTRACT FROM AUTHOR]- Published
- 2024
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26. CD4
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Jian, Lu, Jing, Wu, Feiting, Xie, Jie, Tian, Xinyi, Tang, Hongye, Guo, Jie, Ma, Ping, Xu, Lingxiang, Mao, Huaxi, Xu, and Shengjun, Wang
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B cells ,Full Paper ,HBsAg vaccine ,CD40L ,Full Papers ,extracellular vesicles ,CD4+ T cells - Abstract
T cells secrete bioactive extracellular vesicles (EVs), but the potential biological effects of CD4+ T cell EVs are not clear. The main purpose of this study is to investigate the effects of CD4+ T cell–derived EVs on B cell responses and examine their role in antigen‐mediated humoral immune responses. In this study, CD4+ T cell EVs are purified from activated CD4+ T cells in vitro. After immunization with the Hepatitis B surface antigen (HBsAg) vaccine, CD4+ T cell EVs‐treated mice show stronger humoral immune responses, which is indicated by a greater Hepatitis B surface antibody (HBsAb) level in serum and a greater proportion of plasma cells in bone marrow. In addition, it is found that EVs released from activated CD4+ T cells play an important role in B cell responses in vitro, which significantly promote B cell activation, proliferation, and antibody production. Interestingly, antigen‐specific CD4+ T cell EVs are found to be more efficient than control EVs in enhancing B cell responses. Furthermore, it is shown that CD40 ligand (CD40L) is involved in CD4+ T cell EVs‐mediated B cell responses. Overall, the results have demonstrated that CD4+ T cell EVs enhance B cell responses and serve as a novel immunomodulator to promote antigen‐specific humoral immune responses., CD4+ T cells release bioactive extracellular vesicles. CD4+ T cells extracellular vesicles (EVs) can enhance B cell responses by CD40 ligand (CD40L), which significantly promote B cell activation, proliferation, and antibody production in vitro. In addition, the application of CD4+ T cell EVs further promotes antigen‐specific humoral immune responses in Hepatitis B surface antigen (HBsAg)‐immunized mice.
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- 2018
27. Inhibition of Bruton's tyrosine kinase interferes with pathogenic B-cell development in inflammatory CNS demyelinating disease
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Roxanne Pretzsch, Philipp Haselmayer, Ursula Boschert, Roland Grenningloh, Martin S. Weber, Darius Häusler, Wolfgang Brück, and Sebastian Torke
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Encephalomyelitis, Autoimmune, Experimental ,T-Lymphocytes ,Lymphocyte Activation ,Pathology and Forensic Medicine ,Multiple sclerosis ,Cellular and Molecular Neuroscience ,Mice ,Immune system ,Piperidines ,Bruton’s tyrosine kinase ,medicine ,Agammaglobulinaemia Tyrosine Kinase ,Evobrutinib ,Bruton's tyrosine kinase ,Animals ,Humans ,Protein Kinase Inhibitors ,B cell ,chemistry.chemical_classification ,B-Lymphocytes ,Original Paper ,B cells ,Experimental autoimmune encephalomyelitis ,biology ,BTKi ,Cell Differentiation ,medicine.disease ,CNS DEMYELINATING DISEASE ,Mice, Inbred C57BL ,Enzyme ,medicine.anatomical_structure ,Pyrimidines ,chemistry ,Myeloid cells ,biology.protein ,Cancer research ,Neurology (clinical) ,Tyrosine kinase - Abstract
Anti-CD20-mediated B-cell depletion effectively reduces acute multiple sclerosis (MS) flares. Recent data shows that antibody-mediated extinction of B cells as a lasting immune suppression, harbors the risk of developing humoral deficiencies over time. Accordingly, more selective, durable and reversible B-cell-directed MS therapies are needed. We here tested inhibition of Bruton’s tyrosine kinase (BTK), an enzyme centrally involved in B-cell receptor signaling, as the most promising approach in this direction. Using mouse models of MS, we determined that evobrutinib, the first BTK inhibiting molecule being developed, dose-dependently inhibited antigen-triggered activation and maturation of B cells as well as their release of pro-inflammatory cytokines. Most importantly, evobrutinib treatment functionally impaired the capacity of B cells to act as antigen-presenting cells for the development of encephalitogenic T cells, resulting in a significantly reduced disease severity in mice. In contrast to anti-CD20, BTK inhibition silenced this key property of B cells in MS without impairing their frequency or functional integrity. In conjunction with a recent phase II trial reporting that evobrutinib is safe and effective in MS, our mechanistic data highlight therapeutic BTK inhibition as a landmark towards selectively interfering with MS-driving B-cell properties. Electronic supplementary material The online version of this article (10.1007/s00401-020-02204-z) contains supplementary material, which is available to authorized users.
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- 2020
28. SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells
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Araceli Perez-Lopez, Porfirio Nava, Carlos Samuel Galán-Enríquez, Celia Alpuche-Aranda, Vianney Ortiz-Navarrete, and Abraham García-Gil
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0301 basic medicine ,Inflammasomes ,Interleukin-1beta ,Cell Cycle Proteins ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Salmonella ,NLRC4 ,Phosphorylation ,B-Lymphocytes ,Mice, Inbred BALB C ,Effector ,Pyroptosis ,Inflammasome ,SopB ,Cell biology ,Infectious Diseases ,IL-1β ,030220 oncology & carcinogenesis ,YAP ,Research Paper ,Signal Transduction ,medicine.drug ,Microbiology (medical) ,Immunology ,Down-Regulation ,Biology ,Microbiology ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Bacterial Proteins ,medicine ,Animals ,lcsh:RC109-216 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,B cells ,Microbial Viability ,Akt ,Calcium-Binding Proteins ,YAP-Signaling Proteins ,Phosphoproteins ,Mice, Inbred C57BL ,030104 developmental biology ,Parasitology ,Apoptosis Regulatory Proteins ,Proto-Oncogene Proteins c-akt ,Inflammasome complex - Abstract
B cells are a target of Salmonella infection, allowing bacteria survival without inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and lack of inflammasome complex activation, which impairs the secretion of IL-1β. YAP phosphorylation is required for downregulation of Nlrc4 in B cells during Salmonella infection; however, the microorganism’s mechanisms underlying the inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our findings demonstrate that the Salmonella effector SopB triggers a signaling cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that lack Rictor, or inhibited the signaling cascade using a pharmacological approach, we were able to restore the function of the NLRC4 inflammasome in B cells and the ability to control the infection. Furthermore, B cells from infected mice exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella also triggers this pathway in vivo. In summary, our data demonstrate that the Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt-YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to manipulate the host environment by turning it into a survival niche to establish a successful infection.
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- 2018
29. BAFF and APRIL expression as an autoimmune signature of membranous nephropathy
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Jooyoung Kim, Chun Soo Lim, Hajeong Lee, Sang-Ho Lee, Kwon Wook Joo, Dong Ki Kim, Seung Hee Yang, Hyung Ah Jo, Yon Su Kim, Minkyoung Park, Seung Seok Han, Yun Jung Oh, and Jung Pyo Lee
- Subjects
0301 basic medicine ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Gastroenterology ,Autoimmunity ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Membranous nephropathy ,Internal medicine ,Biopsy ,medicine ,APRIL ,B-cell activating factor ,Autoimmune disease ,Kidney ,B cells ,Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,autoimmunity ,membranous nephropathy ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,BAFF ,business ,Research Paper - Abstract
// Seung Seok Han 1, 2 , Seung Hee Yang 2 , Hyung Ah Jo 1 , Yun Jung Oh 2 , Minkyoung Park 2 , Joo Young Kim 2 , Hajeong Lee 1, 2 , Jung Pyo Lee 1, 2, 3 , Sang-Ho Lee 4 , Kwon Wook Joo 1, 2 , Chun Soo Lim 1, 3 , Yon Su Kim 1, 2 and Dong Ki Kim 1, 2 1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea 2 Kidney Research Institute, Seoul National University, Seoul, Korea 3 Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea 4 Department of Internal Medicine, College of medicine, Kyung Hee University, Seoul, Korea Correspondence to: Dong Ki Kim, email: dkkim73@gmail.com Keywords: APRIL; autoimmunity; BAFF; B cells; membranous nephropathy Received: July 03, 2017 Accepted: November 14, 2017 Published: December 14, 2017 ABSTRACT Background: Based on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN). Results: The plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls. The BAFF levels were higher in relapse cases, whereas the APRIL levels were higher in the patients who did not experience remission compared with the counterpart patients. The ectopic expression of BAFF and APRIL was observed in the glomeruli or circulating B cells of MN patients, and this high expression trend was similar to that of lupus patients. Conclusions: Expression profile of BAFF and APRIL in MN is similar to that of other autoimmune disease, which affects the kidney outcomes. Methods: Plasma BAFF and APRIL levels were measured upon kidney biopsy in patients with primary ( n = 89) and secondary MN ( n = 13), and the results were compared with the levels in healthy controls ( n = 111). The kidney outcomes (e.g., remission and relapse) were traced for the median of 3 years. Aberrant expression of the cytokines was evaluated in the kidney and circulating B cells using immunohistochemistry and flow cytometry analyses, respectively.
- Published
- 2017
30. Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study
- Author
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Kaushik Patra, Soraya Madani, Armando Flor, Gabriela Klodowska-Duda, Mark Agius, Jing Li, Maciej Maciejowski, Eliezer Katz, Andrzej Potemkowski, Gerard Barron, and Jacob Wesley
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Adult ,Male ,medicine.drug_class ,intravenous administration ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Monoclonal antibody ,Placebo ,03 medical and health sciences ,Multiple Sclerosis, Relapsing-Remitting ,0302 clinical medicine ,Pharmacokinetics ,pharmacodynamics ,medicine ,Humans ,030212 general & internal medicine ,Pathophysiology of multiple sclerosis ,subcutaneous administration ,B cells ,Dose-Response Relationship, Drug ,business.industry ,Multiple sclerosis ,Middle Aged ,medicine.disease ,Neurology ,Tolerability ,Inebilizumab ,Pharmacodynamics ,Female ,Neurology (clinical) ,business ,Original Research Papers ,pharmacokinetics ,030217 neurology & neurosurgery - Abstract
Background: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19+ B cells. Objectives: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS. Methods: This phase 1 trial randomised 28 patients 3:1 (21, inebilizumab; 7, placebo) to inebilizumab (2 intravenous (IV) doses, days 1 and 15: 30, 100 or 600 mg; or single subcutaneous (SC) dose on day 1: 60 or 300 mg) or matching placebo, with follow-up until at least week 24 or return of CD19+ B-cell count to ⩾80 cells/µL. Results: Complete B-cell depletion was observed across all doses. Infusion/injection (grade 1/2) reactions occurred in 6/15 patients receiving inebilizumab IV, 2/5 placebo IV and 1/6 inebilizumab SC. Serious adverse events occurred in three patients receiving inebilizumab: pyrexia, mixed-drug intoxication (unrelated to inebilizumab; resulted in death) and urinary tract infection. Mean number of cumulative new gadolinium-enhancing lesions over 24 weeks was 0.1 with inebilizumab versus 1.3 with placebo; mean numbers of new/newly enlarging T2 lesions were 0.4 and 2.4, respectively. Conclusion: Inebilizumab had an acceptable safety profile in relapsing MS patients and showed a trend in reductions in new/newly enlarging and gadolinium-enhancing lesions.
- Published
- 2017
31. A Fix for Fractures.
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BIOPRINTING ,B cells ,CARTILAGE cells ,BONE morphogenetic proteins ,CORD blood ,STEM cell donors - Abstract
The article offers update on bone fracture prevention and treatments for conditions such as osteoporosis. It discusses findings of several research including fracture repair via bone remodeling using osteoclasts, potential of high frequency sound waves to convert bone marrow derived mesenchymal stem cells into bone cells, and a demineralised bone paper biomaterial used to advanced the understanding of bone biology, model disease progression and screen drug responses.
- Published
- 2023
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32. Making the paper: Constantin Polychronakos & Michael German.
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GENETICS , *PANCREATIC secretions , *B cells , *HEREDITY - Abstract
The article discusses various studies regarding the role of a certain gene in the formation of the insulin-producing cells of the pancreas. Geneticist Constantin Polychronakos of McGill University found that each pancreas of a child lacks insulin-producing cells, as though the body had no proper instructions for making them. Michael German of the University of California suggests that Rfx6 expression is one of the earliest genes to be turned on by neurogenin 3.
- Published
- 2010
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33. Human monocyte-derived dendritic cells exposed to hyperthermia show a distinct gene expression profile and selective upregulation of IGFBP6
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Brunangelo Falini, Fabrizio Stracci, Pietro Zoppoli, Maria Concetta Palumbo, Leon A. Bach, Filippo Castiglione, Massimo Conese, Arcangelo Liso, Alessandra Pucciarini, Rosa Trotta, Pasquale De Luca, Matteo Landriscina, Francesca Massenzio, Barbara Bigerna, Giorgina Specchia, Stefano Castellani, Liso, A, Castellani, S, Massenzio, F, Trotta, R, Pucciarini, A, Bigerna, B, De Luca, P, Zoppoli, P, Castiglione, F, Palumbo, Mc, Stracci, F, Landriscina, M, Specchia, G, Bach, La, Conese, M, and Falini, B.
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0301 basic medicine ,medicine.medical_specialty ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,Apoptosis ,B cells ,Chemotaxis ,Dendritic cells ,Hyperthermia ,Immune response ,Immunity ,Immunology and Microbiology Section ,Oncology ,Internal medicine ,medicine ,dendritic cells ,chemotaxis ,B cell ,Innate immune system ,Hematology ,Research Paper: Immunology ,apoptosis ,Apoptosi ,Chemotaxi ,Acquired immune system ,hyperthermia ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,Dendritic cell - Abstract
// Arcangelo Liso 1 , Stefano Castellani 1 , Francesca Massenzio 1 , Rosa Trotta 1 , Alessandra Pucciarini 2 , Barbara Bigerna 2 , Pasquale De Luca 3 , Pietro Zoppoli 4 , Filippo Castiglione 5 , Maria Concetta Palumbo 5 , Fabrizio Stracci 6 , Matteo Landriscina 1,7 , Giorgina Specchia 8 , Leon A. Bach 9,10 , Massimo Conese 1 and Brunangelo Falini 2 1 Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy 2 Institute of Haematology, University of Perugia, Perugia, Italy 3 Stazione Zoologica A. Dohrn, Naples, Italy 4 Dipartimento di Medicina Sperimentale e Clinica, Universita degli Studi Magna Graecia, Catanzaro, Italy 5 Institute for Applied Computing, National Research Council of Italy, Rome, Italy 6 Department of Experimental Medicine, Section of Public Health, University of Perugia, Perugia, Italy 7 Laboratory of Preclinical and Translational Research, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy 8 Institute of Hematology, University of Bari, Bari, Italy 9 Department of Medicine, Alfred Hospital, Monash University, Melbourne, Australia 10 Department of Endocrinology and Diabetes, Alfred Hospital, Melbourne, Australia Correspondence to: Arcangelo Liso, email: // Massimo Conese, email: // Keywords : apoptosis, B cells, chemotaxis, dendritic cells, hyperthermia, Immunology and Microbiology Section, Immune response, Immunity Received : April 16, 2017 Accepted : May 12, 2017 Published : June 01, 2017 Abstract Fever plays a role in activating innate immunity while its relevance in activating adaptive immunity is less clear. Even brief exposure to elevated temperatures significantly impacts on the immunostimulatory capacity of dendritic cells (DCs), but the consequences on immune response remain unclear. To address this issue, we analyzed the gene expression profiles of normal human monocyte-derived DCs from nine healthy adults subjected either to fever-like thermal conditions (39°C) or to normal temperature (37°C) for 180 minutes. Exposure of DCs to 39°C caused upregulation of 43 genes and downregulation of 24 genes. Functionally, the up/downregulated genes are involved in post-translational modification, protein folding, cell death and survival, and cellular movement. Notably, when compared to monocytes, DCs differentially upregulated transcription of the secreted protein IGFBP-6, not previously known to be specifically linked to hyperthermia. Exposure of DCs to 39°C induced apoptosis/necrosis and resulted in accumulation of IGFBP-6 in the conditioned medium at 48 h. IGFBP-6 may have a functional role in the hyperthermic response as it induced chemotaxis of monocytes and T lymphocytes, but not of B lymphocytes. Thus, temperature regulates complex biological DC functions that most likely contribute to their ability to induce an efficient adaptive immune response.
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- 2017
34. MiR-148a impairs Ras/ERK signaling in B lymphocytes by targeting SOS proteins
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Nicole Ludwig, Andreas Keller, Eckart Meese, Petra Leidinger, Julia Alles, Stefanie Rheinheimer, and Friedrich A. Grässer
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0301 basic medicine ,MAPK/ERK pathway ,Reporter gene ,B cells ,microRNA ,Endogeny ,Transfection ,SOS ,Biology ,Molecular biology ,03 medical and health sciences ,ERK ,030104 developmental biology ,medicine.anatomical_structure ,miR-148a ,Oncology ,Immunology ,medicine ,Phosphorylation ,Luciferase ,B cell ,Research Paper - Abstract
// Julia Alles 1 , Nicole Ludwig 1 , Stefanie Rheinheimer 1 , Petra Leidinger 1 , Friedrich A. Grasser 2 , Andreas Keller 3 and Eckart Meese 1 1 Institute of Human Genetics, Saarland University, 66421 Homburg, Germany 2 Institute of Virology, Saarland University, 66421 Homburg, Germany 3 Chair for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany Correspondence to: Julia Alles, email: ju.al@mx.uni-saarland.de Keywords: B cells, microRNA, miR-148a, SOS, ERK Received: March 15, 2017 Accepted: April 24, 2017 Published: May 07, 2017 ABSTRACT Although microRNAs have been recognized as central cellular regulators, there is an evident lack of knowledge about their targets. Here, we analyzed potential target genes for miR-148a functioning in Ras signaling in B cells, including SOS1 and SOS2. A dual-luciferase reporter assay showed significantly decreased luciferase activity upon ectopic overexpression of miR-148a in HEK-293T cells that were co-transfected with the 3′UTR of either SOS1 or SOS2. Each of the 3′UTRs of SOS1 and SOS2 contained two binding sites for miR-148a both of which were necessary for the decreased luciferase activity. MiR-148a overexpression in HEK-293T lead to significantly reduced levels of both endogenous SOS1 and SOS2 proteins. Likewise, reduced levels of SOS proteins were found in two B cell lines that were transfected with miR-148a. The level of ERK1/2 phosphorylation as one of the most relevant downstream members of the Ras/ERK signaling pathway was also reduced in cells with miR-148a overexpression. The data show that miR-148a impairs the Ras/ERK signaling pathway via SOS1 and SOS2 proteins in B cells.
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- 2017
35. Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age
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Maria Pallin, Margaret A. Fischl, Louis Gonzalez, Li Pan, Maria L. Alcaide, Gordon M. Dickinson, Savita Pahwa, Varghese K. George, Stefano Rinaldi, Nicola Cotugno, Rajendra Pahwa, Allan Rodriguez, Paolo Palma, Lesley R. de Armas, Celeste M. Sanchez, and Suresh Pallikkuth
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0301 basic medicine ,Male ,Aging ,HIV Infections ,Antibodies, Viral ,Settore MED/06 ,0302 clinical medicine ,Immunophenotyping ,Influenza A Virus, H1N1 Subtype ,Influenza A Virus ,Viral ,Cellular Senescence ,immunosenescence ,B-Lymphocytes ,Vaccination ,virus diseases ,Immunosenescence ,Middle Aged ,Settore MED/38 ,influenza vaccination ,3. Good health ,PD1 ,medicine.anatomical_structure ,Influenza Vaccines ,Female ,Research Paper ,Cart ,Adult ,Double negative ,Peripheral blood mononuclear cell ,Antibodies ,03 medical and health sciences ,Young Adult ,medicine ,Humans ,H1N1 Subtype ,B cells ,HIV ,aging ,chronic infections ,Aged ,Hemagglutination Inhibition Tests ,Immunologic Memory ,B cell ,business.industry ,Cell Biology ,030104 developmental biology ,Humoral immunity ,Immunology ,business ,030215 immunology - Abstract
Combination antiretroviral therapies (cART) can lead to normal life expectancy in HIV-infected persons, and people aged >50 yrs represent the fastest growing HIV group. Although HIV and aging are independently associated with impaired humoral immunity, immune status in people aging with HIV is relatively unexplored. In this study influenza vaccination was used to probe age associated perturbations in the B cell compartment of HIV-negative “healthy controls” (HC) and virologically controlled HIV-infected participants on cART (HIV) (n=124), grouped by age as young (
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- 2017
36. role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review.
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Shen, Mengni, O'Donnell, Elizabeth, Leon, Gabriela, Kisovar, Ana, Melo, Pedro, Zondervan, Krina, Granne, Ingrid, and Southcombe, Jennifer
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B cells ,ENDOMETRIUM ,AUTOIMMUNITY - Abstract
STUDY QUESTION What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies? SUMMARY ANSWER Endometrial B cells typically constitute <5% of total endometrial CD45
+ lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions, current evidence is inconsistent. WHAT IS KNOWN ALREADY B cells are vitally important in the mucosal immune environment and have been extensively characterized in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs). A comprehensive summary of current data investigating B cells will facilitate our understanding of endometrial B cells in the endometrial mucosal immune environment. STUDY DESIGN, SIZE, DURATION This systematic review retrieved relevant studies from four databases (MEDLINE, EMBASE, Web of Science Core Collection and CINAHL) from database inception until November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The search strategy combined the use of subject headings and relevant text words related to 'endometrium', 'B cells' and B-cell derivatives, such as 'antibody' and 'immunoglobulin'. Non-benign diseases were excluded using cancer-related free-text terms, and searches were limited to the English language and human subjects. Only peer-reviewed research papers were included. Each paper was graded as 'Good', 'Fair' or 'Poor' quality based on the NEWCASTLE-OTTAWA quality assessment scale. Only 'Good' quality papers were included. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-seven studies met the selection criteria and were included in this review: 10 cross-sectional studies investigated B cells in the normal endometrium; and 17 case–control studies compared the characteristics of endometrial B cells in control and benign female reproductive pathologies including endometritis, endometriosis, infertility, abnormal uterine bleeding, endometrial polyps and uterine fibroids. In all studies, B cells were present in the endometrium, scattered or in the form of LAs. CD20+ B cells were more abundant in patients with endometritis, but the data were inconsistent as to whether B-cell numbers were increased in endometriosis and patients with reproductive pathologies. LIMITATIONS, REASONS FOR CAUTION Although only 'good' quality papers were included in this systematic review, there were variations in patients' age, diagnostic criteria for different diseases and sample collection time among included studies. Additionally, a large number of the included studies only used immunohistochemistry as the identification method for endometrial B cells, which may fail to provide an accurate representation of the numbers of endometrial B cells. WIDER IMPLICATIONS OF THE FINDINGS Histological studies found that endometrial B cells are either scattered or surrounded by T cells in LAs: the latter structure seems to be under hormonal control throughout the menstrual cycle and resembles TLSs that have been observed in other tissues. Further characterization of endometrial B cells and LAs could offer insights to endometrial B-cell function, particularly in the context of autoimmune-associated pathologies, such as endometriosis. Additionally, clinicians should be aware of the limited value of diagnosing plasma cell infiltration using only CD138. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Finox Biotech. The authors have no conflicts of interest to declare. PROSPERO REGISTRATION NUMBER This systematic review was registered in PROSPERO in January 2020 (PROSPERO ID: CRD42020152915). [ABSTRACT FROM AUTHOR]- Published
- 2022
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37. B cells in head and neck squamous cell carcinoma: current opinion and novel therapy.
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Guo, Xinyue, Xu, Licheng, Nie, Luan, Zhang, Chenyu, Liu, Yaohui, Zhao, Rui, Cao, Jing, Tian, Linli, and Liu, Ming
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B cells ,SQUAMOUS cell carcinoma ,IMMUNE checkpoint inhibitors ,T cells ,TUMOR microenvironment ,RADIOTHERAPY - Abstract
Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumour. Despite advancements in surgery, radiotherapy and chemotherapy, which have improved the prognosis of most patients, a subset of patients with poor prognoses still exist due to loss of surgical opportunities, postoperative recurrence, and metastasis, among other reasons. The tumour microenvironment (TME) is a complex organization composed of tumour, stromal, and endothelial cells. Communication and interaction between tumours and immune cells within the TME are increasingly being recognized as pivotal in inhibiting or promoting tumour development. Previous studies on T cells in the TME of HNSCC have yielded novel therapeutic possibilities. However, the function of B cells, another adaptive immune cell type, in the TME of HNSCC patients has yet to be determined. Recent studies have revealed various distinct subtypes of B cells and tertiary lymphoid structures (TLSs) in the TME of HNSCC patients, which are believed to impact the efficacy of immune checkpoint inhibitors (ICIs). Therefore, this paper focuses on B cells in the TME to explore potential directions for future immunotherapy for HNSCC. [ABSTRACT FROM AUTHOR]
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- 2024
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38. The Roles of Various Immune Cell Populations in Immune Response against Helminths.
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Lekki-Jóźwiak, Janina and Bąska, Piotr
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CELL populations ,IMMUNE response ,B cells ,INNATE lymphoid cells ,HELMINTHS ,HELMINTHIASIS ,KNOWLEDGE gap theory - Abstract
Helminths are multicellular parasites that are a substantial problem for both human and veterinary medicine. According to estimates, 1.5 billion people suffer from their infection, resulting in decreased life quality and burdens for healthcare systems. On the other hand, these infections may alleviate autoimmune diseases and allergy symptoms. The immune system is programmed to combat infections; nevertheless, its effector mechanisms may result in immunopathologies and exacerbate clinical symptoms. This review summarizes the role of the immune response against worms, with an emphasis on the Th
2 response, which is a hallmark of helminth infections. We characterize non-immune cells (enteric tuft cells—ETCs) responsible for detecting parasites, as well as the role of hematopoietic-derived cells (macrophages, basophils, eosinophils, neutrophils, innate lymphoid cells group 2—ILC2s, mast cells, T cells, and B cells) in initiating and sustaining the immune response, as well as the functions they play in granulomas. The aim of this paper is to review the existing knowledge regarding the immune response against helminths, to attempt to decipher the interactions between cells engaged in the response, and to indicate the gaps in the current knowledge. [ABSTRACT FROM AUTHOR]- Published
- 2024
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39. The Research Progress on Immortalization of Human B Cells.
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Xu, Huiting, Xiang, Xinxin, Ding, Weizhe, Dong, Wei, and Hu, Yihong
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MONOCLONAL antibodies ,B cells ,IMMUNOGLOBULIN producing cells ,SV40 (Virus) ,VIRUS diseases ,EPSTEIN-Barr virus - Abstract
Human B cell immortalization that maintains the constant growth characteristics and antibody expression of B cells in vitro is very critical for the development of antibody drugs and products for the diagnosis and bio-therapeutics of human diseases. Human B cell immortalization methods include Epstein-Barr virus (EBV) transformation, Simian virus 40 (SV40) virus infection, in vitro genetic modification, and activating CD40, etc. Immortalized human B cells produce monoclonal antibodies (mAbs) very efficiently, and the antibodies produced in this way can overcome the immune rejection caused by heterologous antibodies. It is an effective way to prepare mAbs and an important method for developing therapeutic monoclonal antibodies. Currently, the US FDA has approved more than 100 mAbs against a wide range of illnesses such as cancer, autoimmune diseases, infectious diseases, and neurological disorders. This paper reviews the research progress of human B cell immortalization, its methods, and future directions as it is a powerful tool for the development of monoclonal antibody preparation technology. [ABSTRACT FROM AUTHOR]
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- 2023
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40. B lymphocytes as direct antigen-presenting cells for anti-tumor DNA vaccines
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Viswa Teja Colluru and Douglas G. McNeel
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CD4-Positive T-Lymphocytes ,DNA vaccine ,0301 basic medicine ,Antigen-Presenting Cells ,CD8-Positive T-Lymphocytes ,Biology ,Cancer Vaccines ,DNA vaccination ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Plasmid ,Antigen ,Cell Line, Tumor ,Vaccines, DNA ,Animals ,Humans ,Cytotoxic T cell ,Immune response ,Antigen-presenting cell ,Mice, Knockout ,Antigen Presentation ,B-Lymphocytes ,B cells ,Immunogenicity ,Research Paper: Immunology ,Immunity ,Cross-presentation ,DNA ,Dendritic Cells ,Virology ,Coculture Techniques ,3. Good health ,Mice, Inbred C57BL ,direct presentation ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Immunology and Microbiology Section ,Sarcoma, Experimental ,Plasmids - Abstract
// Viswa Teja Colluru 1,2 and Douglas G. McNeel 1,2 1 Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA 2 Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA Correspondence to: Douglas G. McNeel, email: // Keywords : DNA vaccine, B cells, dendritic cells, direct presentation, Immunology and Microbiology Section, Immune response, Immunity Received : July 26, 2016 Accepted : September 16, 2016 Published : September 21, 2016 Abstract In spite of remarkable preclinical efficacy, DNA vaccination has demonstrated low immunogenicity in humans. While efforts have focused on increasing cross-presentation of DNA-encoded antigens, efforts to increase DNA vaccine immunogenicity by targeting direct presentation have remained mostly unexplored. In these studies, we compared the ability of different APCs to present antigen to T cells after simple co-culture with plasmid DNA. We found that human primary peripheral B lymphocytes, and not monocytes or in vitro derived dendritic cells (DCs), were able to efficiently encode antigen mRNA and expand cognate tumor antigen-specific CD8 T cells ex vivo . Similarly, murine B lymphocytes co-cultured with plasmid DNA, and not DCs, were able to prime antigen-specific T cells in vivo. Moreover, B lymphocyte-mediated presentation of plasmid antigen led to greater Th1-biased immunity and was sufficient to elicit an anti-tumor effect in vivo . Surprisingly, increasing plasmid presentation by B cells, and not cross presentation of peptides by DCs, further augmented traditional plasmid vaccination. Together, these data suggest that targeting plasmid DNA to B lymphocytes, for example through transfer of ex vivo plasmidloaded B cells, may be novel means to achieve greater T cell immunity from DNA vaccines.
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- 2016
41. Inflammatory and immune markers associated with physical frailty syndrome: findings from Singapore longitudinal aging studies
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Liang Feng, Hassen Kared, Yanxia Lu, Tze Pin Ng, Anis Larbi, Tamas Fulop, Crystal Tze Ying Tan, Xavier Camous, Esther Wing Hei Mok, and Ma Shwe Zin Nyunt
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Male ,frailty risk ,0301 basic medicine ,Aging ,Cellular immunity ,Frail Elderly ,T cell ,Frailty syndrome ,Pilot Projects ,Inflammation ,CD38 ,03 medical and health sciences ,Research Paper: Gerotarget (Focus on Aging) ,Immune system ,Humans ,Medicine ,Longitudinal Studies ,Aged ,immunosenescence ,Singapore ,B cells ,Frailty ,Gerotarget ,business.industry ,Immunosenescence ,Middle Aged ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Immunology ,Female ,medicine.symptom ,business ,T cell subsets ,CD8 - Abstract
// Yanxia Lu 1 , Crystal Tze Ying Tan 2 , Ma Shwe Zin Nyunt 3 , Esther Wing Hei Mok 2 , Xavier Camous 2 , Hassen Kared 2 , Tamas Fulop 4 , Liang Feng 5 , Tze Pin Ng 3,* and Anis Larbi 2,4* 1 Department of Clinical Psychology and Psychiatry/School of Public Health, Zhejiang University College of Medicine, Hangzhou, China 2 Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 3 Gerontology Research Programme, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 4 Geriatrics Division, Department of Medicine, Research Center on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada 5 Graduate Medical School, Duke-National University of Singapore, Singapore * These authors have contributted equally to this work Correspondence to: Anis Larbi, email: // Keywords : inflammation; immunosenescence; frailty risk; T cell subsets; B cells; Gerotarget Received : November 18, 2015 Accepted : April 10, 2016 Published : April 22, 2016 Abstract Chronic systematic inflammation and reduced immune system fitness are considered potential contributing factors to the development of age-related frailty, but the underlying mechanisms are poorly defined. This exploratory study aimed to identify frailty-related inflammatory markers and immunological phenotypes in a cohort of community-dwelling adults aged ≥ 55 years. Frailty was assessed using two models, a Frailty Index and a categorical phenotype, and correlated with levels of circulating immune biomarkers and markers of senescence in immune cell subsets. We identified eight serological biomarkers that were associated with frailty, including sgp130, IL-2Rα, I-309, MCP-1, BCA-1, RANTES, leptin, and IL-6R. Frailty Index was inversely predicted by the frequency of CD3+, CD45RA+, and central memory CD4 cells, and positively predicted by the loss of CD28 expression, especially in CD8+ T cells, while frailty status was predicted by the frequency of terminal effector CD8+ T cells. In γ/δ T cells, frailty was negatively associated with CD27, and positively associated with IFNγ+TNFα- secretion by γ/δ2+ cells and IFNγ-TNFα+ secretion by γ/δ2- cells. Increased numbers of exhausted and CD38+ B cells, as well as CD14+CD16+ inflammatory monocytes, were also identified as frailty-associated phenotypes. This pilot study supports an association between inflammation, cellular immunity, and the process of frailty. These findings have significance for the early identification of frailty using circulating biomarkers prior to clinical manifestations of severe functional decline in the elderly.
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- 2016
42. PAX5A and PAX5B isoforms are both efficient to drive B cell differentiation
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Bastien Gerby, Stéphane J. C. Mancini, Marine Dubois, Laurent Delpy, Michel Cogné, Cyril Broccardo, Laura Jamrog, Naïs Prade, Nelly Rouquié, Charlotte Cresson, Sylvie Hébrard, Stéphanie Lagarde, Eric Delabesse, Sophie Péron, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Hématologie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hématologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherches en Cancérologie de Toulouse (CRCT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Gerby, Bastien, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)
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0301 basic medicine ,Gene isoform ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,acute lymphoblastic leukemia ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Biology ,03 medical and health sciences ,Exon ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,hemic and lymphatic diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,B cell development ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,medicine ,Gene ,Transcription factor ,B cell ,transcription factor ,ComputingMilieux_MISCELLANEOUS ,Pax5 ,B cells ,Promoter ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,PAX5 ,Ex vivo ,Research Paper - Abstract
International audience; Pax5 is the guardian of the B cell identity since it primes or enhances the expression of B cell specific genes and concomitantly represses the expression of B cell inappropriate genes. The tight regulation of Pax5 is therefore required for an efficient B cell differentiation. A defect in its dosage can translate into immunodeficiency or malignant disorders such as leukemia or lymphoma. Pax5 is expressed from two different promoters encoding two isoforms that only differ in the sequence of their first alternative exon. Very little is known regarding the role of the two isoforms during B cell differentiation and the regulation of their expression. Our work aims to characterize the mechanisms of regulation of the expression balance of these two isoforms and their implication in the B cell differentiation process using murine ex vivo analyses. We show that these two isoforms are differentially regulated but have equivalent function during early B cell differentiation and may have functional differences after B cell activation. The tight control of their expression may thus reflect a way to finely tune Pax5 dosage during B cell differentiation process.
- Published
- 2018
43. Characterization of recombinant wild-type and nontoxigenic protein A from Staphylococcus pseudintermedius
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Abouelkhair, Mohamed A., Bemis, David A., and Kania, Stephen A.
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0301 basic medicine ,Staphylococcus pseudintermedius ,Staphylococcus ,Apoptosis ,law.invention ,0403 veterinary science ,law ,vaccine ,Dog Diseases ,skin and connective tissue diseases ,B-Lymphocytes ,biology ,04 agricultural and veterinary sciences ,Staphylococcal Infections ,Antimicrobial ,Antibodies, Bacterial ,Recombinant Proteins ,Infectious Diseases ,Recombinant DNA ,Research Paper ,Microbiology (medical) ,040301 veterinary sciences ,Immunology ,Pyoderma ,Virulence ,Microbiology ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Opportunistic pathogen ,Dogs ,Bacterial Proteins ,parasitic diseases ,medicine ,Animals ,lcsh:RC109-216 ,Staphylococcal Protein A ,immune evasion ,B cells ,Wild type ,medicine.disease ,biology.organism_classification ,virulence ,030104 developmental biology ,biology.protein ,Protein A ,Parasitology ,SpsQ - Abstract
Background:Staphylococcus pseudintermedius is an opportunistic pathogen that is the major cause of pyoderma affecting dogs. Conventional antimicrobial treatment for infections caused by this organism have failed in recent years due to widespread resistance and alternative treatment strategies are a high priority. Protein A encoded in Staphylococcus aureus by spa protects the bacterium by binding IgG and acts as a superantigen. Staphylococcus pseudintermedius possess two genes orthologous to S. aureus spa, spsP, and spsQ. Methods: SpsQ and SpsQ-M, a non-toxigenic SpsQ, were cloned and expressed as recombinant proteins and their cytotoxic effect on canine B cells was measured. The neutralizing ability of antibody raised against them in clinically healthy dogs was evaluated. Results: S. pseudintermedius SpsQ induced apoptosis of canine B cells. Specific amino acid substitutions diminished SpsQ-M binding to immunoglobulin and its super-antigenic activity, while its antigenicity was maintained. This recombinant, non-toxigenic S. pseudintermedius SpsQ stimulated the production of antibodies in dogs that specifically reacted with SpsQ and greatly diminished its cytotoxic effect on canine B cells. Conclusions: The production of neutralizing antibody suggests that attenuated, non-toxic SpsQ produced in this study is a good candidate for inclusion in a vaccine for use in the treatment and prevention of S. pseudintermedius infections. Abbreviations: SpA: Staphylococcus aureus protein A; SpsP: Staphylococcus pseudintermedius protein A; SpsQ: Staphylococcus pseudintermedius protein A; SpsQ-M: attenuated Staphylococcus pseudintermedius protein A; MRSP: methicillin resistant Staphylococcus pseudintermedius; IgA: immunoglobulin A; IgG: immunoglobulin G; IgM: immunoglobulin M; VH: variable region of immunoglobulin heavy chain; IgBD: immunoglobulin binding domains; MFI: mean fluorescent intensity; SEM: standard error of the mean; PBMC: Peripheral blood mononuclear cells; CD21: complement receptor type 2; ST: Sequence type; OD: Optical density; ORF: open reading frame; PBS: Phosphate buffered saline; Tween 20: Polyethylene glycol sorbitan monolaurate 20; HRP: horseradish peroxidase; TMB- 3,3',5,5'-Tetramethylbenzidine
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- 2018
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44. Proteoglycan expression correlates with the phenotype of malignant and non-malignant EBV-positive B-cell lines
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Ingemar Ernberg, Liudmila Matskova, Alexandra Y. Tsidulko, Lidiia Astakhova, and Elvira V. Grigorieva
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Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Blotting, Western ,Perlecan ,heparan sulfate biosynthesis ,Real-Time Polymerase Chain Reaction ,lymphoma development ,Extracellular matrix ,Cell Line, Tumor ,medicine ,Epstein-Barr virus ,Humans ,Serglycin ,B cell ,B cells ,B-Lymphocytes ,proteoglycan ,biology ,Biglycan ,Flow Cytometry ,Burkitt Lymphoma ,Virus Latency ,Cell biology ,carbohydrates (lipids) ,Fibronectin ,Cell Transformation, Neoplastic ,Phenotype ,medicine.anatomical_structure ,Oncology ,Biochemistry ,Proteoglycan ,biology.protein ,Versican ,Proteoglycans ,Research Paper - Abstract
The involvement of proteoglycans (PGs) in EBV-host interactions and lymphomagenesis remains poorly investigated. In this study, expression of major proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, aggrecan, NG2, serglycin, decorin, biglycan, lumican, CD44), heparan sulphate (HS) metabolic system (EXT1/2, NDST1/2, GLCE, HS2ST1, HS3ST1/2, HS6ST1/2, SULF1/2, HPSE) and extracellular matrix (ECM) components (collagen 1A1, fibronectin, elastin) in primary B cells and EBV carrying cell lines with different phenotypes, patterns of EBV-host cell interaction and viral latency stages (type I-III) was investigated. Primary B cells expressed a wide repertoire of PGs (dominated by serglycin and CD44) and ECM components. Lymphoblastoid EBV+ B cell lines (LCLs) showed specific PG expression with down-regulation of CD44 and ECM components and up-regulation of serglycin and perlecan/HSPG2. For Burkitt's lymphoma cells (BL), serglycin was down-regulated in BL type III cells and perlecan in type I BL cells. The biosynthetic machinery for HS was active in all cell lines, with some tendency to be down-regulated in BL cells. 5'-aza-dC and/or Trichostatin A resulted in transcriptional upregulation of the genes, suggesting that low expression of ECM components, proteoglycan core proteins and HS biosynthetic system is due to epigenetic suppression in type I cells. Taken together, our data show that proteoglycans are expressed in primary B lymphocytes whereas they are not or only partly expressed in EBV-carrying cell lines, depending on their latency type program.
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- 2015
45. Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins
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Zitao Li, Suihua Lao, Sifei Yu, Binyan Yang, Xiaoying Fu, and Changyou Wu
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Male ,CD3 Complex ,Receptors, Antigen, T-Cell, alpha-beta ,immunoglobulins ,Cell Separation ,Immunophenotyping ,IL-21 ,Medicine ,Cells, Cultured ,B-Lymphocytes ,biology ,Research Paper: Immunology ,hemic and immune systems ,Tuberculosis, Pleural ,Middle Aged ,Flow Cytometry ,Natural killer T cell ,NKT cells ,Phenotype ,tuberculosis ,Oncology ,Immunology and Microbiology Section ,Female ,Antibody ,Signal Transduction ,Adult ,Receptors, CXCR5 ,CD40 Ligand ,CD1 ,chemical and pharmacologic phenomena ,Young Adult ,Immune system ,Antigen ,Paracrine Communication ,Humans ,Organ donation ,Immune response ,Aged ,B cells ,Antigens, Bacterial ,CD40 ,business.industry ,Interleukins ,Immunity ,Mycobacterium tuberculosis ,Virology ,Immunoglobulin G ,Immunoglobulin A, Secretory ,Immunology ,biology.protein ,Natural Killer T-Cells ,business ,Immunologic Memory - Abstract
// Changyou Wu 1 , Zitao Li 1 , Xiaoying Fu 1 , Sifei Yu 1 , Suihua Lao 2 and Binyan Yang 1 1 Institute of Immunology, Zhongshan School of Medicine, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-Sen University, Guangzhou, China 2 Chest Hospital of Guangzhou, Guangzhou, China Correspondence to: Changyou Wu, email: // Keywords : NKT cells, tuberculosis, IL-21, B cells, immunoglobulins, Immunology and Microbiology Section, Immune response, Immunity Received : July 13, 2015 Accepted : September 05, 2015 Published : September 21, 2015 Abstract Natural killer T (NKT) cells from mouse and human play an important role in the immune responses against Mycobacterium tuberculosis . However, the function of CD3 + TCRvβ11 + NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that after stimulation with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN-γ, TNF-α, IL-2 and IL-17. IL-21-expressing NKT cells in PFMCs displayed effector memory phenotype, expressing CD45RO high CD62L low CCR7 low . Moreover, NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co-expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD3 + TCRvβ11 + NKT cells. Sorted CD3 + TCRvβ11 + NKT cells from PFMCs produced IFN-γ and IL-21 after stimulation, which expressed CD40L. Importantly, CD3 + TCRvβ11 + NKT cells provided help to B cells for the production of IgG and IgA. Taken together, our data demonstrate that CD3 + TCRvβ11 + NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection.
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- 2015
46. Genome-wide analysis of p53 transcriptional programs in B cells upon exposure to genotoxic stress in vivo
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Marco J. Morelli, Stefano Campaner, Arianna Sabò, Luca Rotta, Bruno Amati, Claudia Tonelli, Salvatore Bianchi, and Thelma Capra
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p53 ,Cell type ,Genotype ,Transcription, Genetic ,Biology ,Animals ,RNA, Messenger ,Promoter Regions, Genetic ,Enhancer ,Gene ,Transcription factor ,Cells, Cultured ,Mice, Knockout ,Regulation of gene expression ,Genetics ,B-Lymphocytes ,B cells ,Binding Sites ,Gene Expression Profiling ,Promoter ,Chromatin ,Cell biology ,Mice, Inbred C57BL ,Gene expression profiling ,Phenotype ,Gene Expression Regulation ,Oncology ,DNA damage ,chromatin ,Tumor Suppressor Protein p53 ,transcription ,Whole-Body Irradiation ,Genome-Wide Association Study ,Protein Binding ,Priority Research Paper - Abstract
The tumor suppressor p53 is a transcription factor that coordinates the cellular response to DNA damage. Here we provide an integrated analysis of p53 genomic occupancy and p53-dependent gene regulation in the splenic B and non-B cell compartments of mice exposed to whole-body ionizing radiation, providing insight into general principles of p53 activity in vivo. In unstressed conditions, p53 bound few genomic targets; induction of p53 by ionizing radiation increased the number of p53 bound sites, leading to highly overlapping profiles in the different cell types. Comparison of these profiles with chromatin features in unstressed B cells revealed that, upon activation, p53 localized at active promoters, distal enhancers, and a smaller set of unmarked distal regions. At promoters, recognition of the canonical p53 motif as well as binding strength were associated with p53-dependent transcriptional activation, but not repression, indicating that the latter was most likely indirect. p53-activated targets constituted the core of a cell type-independent response, superimposed onto a cell type-specific program. Core response genes included most of the known p53-regulated genes, as well as many new ones. Our data represent a unique characterization of the p53-regulated response to ionizing radiation in vivo.
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- 2015
47. Exploring the Significance of Immune Checkpoints and EBV Reactivation in Antibody Deficiencies with Near-Normal Immunoglobulin Levels or Hyperimmunoglobulinemia.
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Mertowska, Paulina, Mertowski, Sebastian, Smolak, Konrad, Pasiarski, Marcin, Smok-Kalwat, Jolanta, Góźdź, Stanisław, and Grywalska, Ewelina
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RESEARCH ,IMMUNE checkpoint inhibitors ,IMMUNOGLOBULINS ,GENETICS ,B cells ,MEVALONATE kinase deficiency ,IMMUNOLOGICAL deficiency syndromes ,RESEARCH funding ,HEMATOLOGIC malignancies ,T cells ,EPSTEIN-Barr virus diseases ,DISEASE complications - Abstract
Simple Summary: This article addresses the topic of primary immunodeficiencies, with particular emphasis on antibody deficiencies with near-normal immunoglobulin levels or hyperimmunoglobulinemia. This paper goes beyond genetics and emphasizes the importance of the immune system and particularly immune checkpoints and Epstein–Barr virus (EBV) reactivation in the context of these disorders. The article delves into the immune dysregulations occurring in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical picture of patients and, in the future, may contribute to the development of cancer, especially those related to hematological malignancies. Disturbances observed in the immunopathogenesis of the presented diseases go beyond the accepted scheme, with the development of PID largely associated only with genetic disorders, and the article emphasizes that the regulation of immunity and virus reactivation also contributes to the progression of PID. This study delves into the intricate landscape of primary immunodeficiencies, with a particular focus on antibody deficiencies characterized by near-normal immunoglobulin levels or hyperimmunoglobulinemia. Contrary to the conventional focus on genetic dysregulation, these studies investigate the key roles of immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, on selected subpopulations of T and B lymphocytes and their serum concentrations of soluble forms in patients recruited for the studies in healthy volunteers. In addition, the studies also show the role of Epstein–Barr virus (EBV) reactivation and interactions with tested pathways of immune checkpoints involved in the immunopathogenesis of this disease. By examining the context of antibody deficiencies, this study sheds light on the nuanced interplay of factors beyond genetics, particularly the immune dysregulations that occur in the course of this type of disease and the potential role of EBV reactivation, which affects the clinical presentation of patients and may contribute to the development of cancer in the future, especially related to hematological malignancies. [ABSTRACT FROM AUTHOR]
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- 2023
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48. Effect of Impaired B-Cell and CTL Functions on HIV-1 Dynamics.
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AlShamrani, Noura H., Halawani, Reham H., and Elaiw, Ahmed M.
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B cells ,GLOBAL asymptotic stability ,CYTOTOXIC T cells ,HIV ,VIRAL transmission ,HOPFIELD networks - Abstract
This paper formulates and analyzes two mathematical models that describe the within-host dynamics of human immunodeficiency virus type 1 (HIV-1) with impairment of both cytotoxic T lymphocytes (CTLs) and B cells. Both viral transmission (VT) and cellular infection (CT) mechanisms are considered. The second model is a generalization of the first model that includes distributed time delays. For the two models, we establish the non-negativity and boundedness of the solutions, find the basic reproductive numbers, determine all possible steady states and establish the global asymptotic stability properties of all steady states by means of the Lyapunov method. We confirm the theoretical results by conducting numerical simulations. We conduct a sensitivity analysis to show the effect of the values of the parameters on the basic reproductive number. We discuss the results, showing that impaired B cells and CTLs, time delay and latent CT have significant effects on the HIV-1 dynamics. [ABSTRACT FROM AUTHOR]
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- 2023
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49. The relationship between coping self-efficacy and B cells in breast cancer patients.
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El-Amir, Azza, El-Baiomy, Eman M., Sabry, Noha A., Kassem, Loay, Chesney, Margaret A., and Wallston, Kenneth A.
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B cell lymphoma ,CANCER patients ,SELF-efficacy ,CELLULAR immunity ,CANCER diagnosis - Abstract
Background: Breast cancer is the most common tumor among women throughout the world. Diagnosis and treatment of breast cancer are associated with stress and depression. Self-efficacy is one of the most important personal characteristics, studied in cancer, and is correlated with depression and immunity. The aim of the study is as follows: 1. Examining the correlation between coping self-efficacy with depression, DHEA levels, and immunity 2. Examining the correlation between depression and DHEA levels 3. Studying the effect of depression and DHEA levels on immunity 4. Examining the intermediate effect of DHEA levels on the correlation between coping self-efficacy and immunity Methods: Thirty newly diagnosed breast cancer patients recruited from the Oncology Department, Kasr EL-Aini, Cairo University (ages 51.40 + 8.24 years) responded to two questionnaires: Coping Self-Efficacy Scale (CSES) and Patient Health Questionnaire-9 (PHQ-9); blood samples were collected to measure the phenotype of patients' cellular immunity and DHEA levels by flowcytometry and ELISA technique. Results: There was a significant negative correlation between CSES and PHQ-9, a significant positive correlation between PHQ-9 and B-cell count, and there is a significant negative correlation between CSES and B-cell count. The presence of DHEA has no mediatory role on correlation between CSES and B-cell count. Conclusion: This paper presents a new model of psychoneuroimmunology by suggesting an effect of coping self-efficacy on immunity against breast cancer patients. [ABSTRACT FROM AUTHOR]
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- 2023
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50. Inferring linear-B cell epitopes using 2-step metaheuristic variant-feature selection using genetic algorithm.
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Angaitkar, Pratik, Aljrees, Turki, Kumar Pandey, Saroj, Kumar, Ankit, Janghel, Rekh Ram, Sahu, Tirath Prasad, Singh, Kamred Udham, and Singh, Teekam
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B cells ,GENETIC algorithms ,METAHEURISTIC algorithms ,EPITOPES ,FEATURE selection ,SUPPORT vector machines ,AMINO acid sequence - Abstract
Linear-B cell epitopes (LBCE) play a vital role in vaccine design; thus, efficiently detecting them from protein sequences is of primary importance. These epitopes consist of amino acids arranged in continuous or discontinuous patterns. Vaccines employ attenuated viruses and purified antigens. LBCE stimulate humoral immunity in the body, where B and T cells target circulating infections. To predict LBCE, the underlying protein sequences undergo a process of feature extraction, feature selection, and classification. Various system models have been proposed for this purpose, but their classification accuracy is only moderate. In order to enhance the accuracy of LBCE classification, this paper presents a novel 2-step metaheuristic variant-feature selection method that combines a linear support vector classifier (LSVC) with a Modified Genetic Algorithm (MGA). The feature selection model employs mono-peptide, dipeptide, and tripeptide features, focusing on the most diverse ones. These selected features are fed into a machine learning (ML)-based parallel ensemble classifier. The ensemble classifier combines correctly classified instances from various classifiers, including k-Nearest Neighbor (kNN), random forest (RF), logistic regression (LR), and support vector machine (SVM). The ensemble classifier came up with an impressively high accuracy of 99.3% as a result of its work. This accuracy is superior to the most recent models that are considered to be state-of-the-art for linear B-cell classification. As a direct consequence of this, the entire system model can now be utilised effectively in real-time clinical settings. [ABSTRACT FROM AUTHOR]
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- 2023
- Full Text
- View/download PDF
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