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Regulatory B cell

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https://www.readbyqxmd.com/read/29643191/cd83-antibody-inhibits-human-b-cell-responses-to-antigen-as-well-as-dendritic-cell-mediated-cd4-t-cell-responses
#1
Kuan Y Wong, Rebecca Baron, Therese A Seldon, Martina L Jones, Alison M Rice, David J Munster
Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83+ human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29643074/nucleus-specific-expression-in-the-multinuclear-mushroom-forming-fungus-agaricus-bisporus-reveals-different-nuclear-regulatory-programs
#2
Thies Gehrmann, Jordi F Pelkmans, Robin A Ohm, Aurin M Vos, Anton S M Sonnenberg, Johan J P Baars, Han A B Wösten, Marcel J T Reinders, Thomas Abeel
Many fungi are polykaryotic, containing multiple nuclei per cell. In the case of heterokaryons, there are different nuclear types within a single cell. It is unknown what the different nuclear types contribute in terms of mRNA expression levels in fungal heterokaryons. Each cell of the mushroom Agaricus bisporus contains two to 25 nuclei of two nuclear types originating from two parental strains. Using RNA-sequencing data, we assess the differential mRNA contribution of individual nuclear types and its functional impact...
April 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29628927/evaluating-human-immune-responses-for-vaccine-development-in-a-novel-human-spleen-cell-engrafted-nod-scid-il2r%C3%AE-null-mouse-model
#3
Stéphanie Ghosn, Soulaima Chamat, Eric Prieur, Antoine Stephan, Pierre Druilhe, Hasnaa Bouharoun-Tayoun
The lack of preclinical models able to faithfully predict the immune responses which are later obtained in the clinic is a major hurdle for vaccines development as it increases markedly the delays and the costs required to perform clinical studies. We developed and evaluated the relevance to human immune responses of a novel humanized mouse model, humanized-spleen cells-NOD-SCID-gamma null (Hu-SPL-NSG), in which we grafted human spleen cells in immunodeficient NOD-SCID-IL-2rγnull (NSG) mice. We selected the malaria vaccine candidate, Liver Stage Antigen 3-Full Length, because we had previously observed a major discrepancy between preclinical and clinical results, and compared its immunogenicity with that of a shorter form of the molecule, LSA3-729...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29625982/the-protease-clpxp-and-the-pas-domain-protein-divl-regulate-ctra-and-gene-transfer-agent-production-in-rhodobacter-capsulatus
#4
A B Westbye, L Kater, C Wiesmann, H Ding, C K Yip, J T Beatty
Several members of the Rhodobacterales ( Alphaproteobacteria ) produce a conserved horizontal gene transfer vector, called gene transfer agent (GTA), that appears to have evolved from a bacteriophage. The model system to study GTA biology is the R. capsulatus GTA (RcGTA), a small, tailed bacteriophage-like particle produced by a subset of the cells in a culture. The response regulator CtrA is conserved in the Alphaproteobacteria and is an essential regulator of RcGTA production: it controls production and maturation of the RcGTA particle and RcGTA release from cells...
April 6, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29625123/expression-profiling-of-c-kit-and-its-impact-after-esirna-silencing-during-gonadal-development-in-catfish
#5
C Laldinsangi, B Senthilkumaran
C-kit receptor is a member of a family of growth factor receptors that have tyrosine kinase activity, and are involved in the transduction of growth regulatory signals across plasma membrane by activation of its ligand, kitl/scf. The present study analysed mRNA and protein expression profiles of c-kit in the gonads of catfish, Clarias gariepinus, using real time PCR, in situ hybridization and immunohistochemistry. Tissue distribution analysis revealed higher expression mainly in the catfish gonads. Ontogeny studies showed minimal expression during early developmental stages and highest during 50-75 days post hatch, and the dimorphic expression in gonads decreased gradually till adulthood, which might suggest an important role for this gene around later stages of sex differentiation and gonadal development...
April 3, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29625086/tr1-responses-are-elevated-in-asymptomatic-h-pylori-infected-individuals-and-are-functionally-impaired-in-h-pylori-gastric-cancer-patients
#6
Zongchang Song, Tongxia Zhang, Guang Li, Ying Tang, Yan Luo, Genhua Yu
Gastric cancer is one of the most lethal malignancies worldwide. Chronic Helicobacter pylori (H. pylori) infection can induce an inflammatory response that promotes atrophic gastritis, a preceding event to cancer development. The type 1 regulatory T (Tr1) cells have recently emerged as a critical participant in maintaining self-tolerance. In this study, we examined Tr1 cells in H. pylori infection and gastric cancer development. While H. pylori-uninfected (uninfected) subjects presented low Tr1 frequency in the peripheral blood, H...
April 3, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29622726/morphogen-gradient-reconstitution-reveals-hedgehog-pathway-design-principles
#7
Pulin Li, Joseph S Markson, Sheng Wang, Siheng Chen, Vipul Vachharajani, Michael B Elowitz
In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision remain unclear. Here, combining cell-based in vitro gradient reconstitution, genetic re-wiring, and mathematical modeling, we systematically analyzed the unique architectural features of the Sonic Hedgehog pathway. The combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared to alternative designs...
April 5, 2018: Science
https://www.readbyqxmd.com/read/29620951/car-t-cells-in-trials-recent-achievements-and-challenges-that-remain-in-the-production-of-modified-t-cells-for-clinical-applications
#8
Ulrike Köhl, Stanislava Arsenieva, Astrid Holzinger, Hinrich Abken
The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is attracting growing interest for the treatment of malignant diseases. Early trials with anti-CD19 CAR T cells have achieved spectacular remissions in B-cell leukemia and lymphoma, so far refractory, very recently resulting in the Food and Drug Administration approval of CD19 CAR T cells for therapy. With further applications and increasing numbers of patients, the reproducible manufacture of high-quality clinical-grade CAR T cells is becoming an ever greater challenge...
April 5, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29620276/microrna%C3%A2-148a-inhibition-protects-against-ovariectomy%C3%A2-induced-osteoporosis-through-pi3k-akt-signaling-by-estrogen-receptor-%C3%AE
#9
Yu Xiao, Bing Li, Jun Liu
The present study aimed to investigate the effect of microRNA‑148a downregulation on osteoporosis by using an ovariectomized rat model. Reverse transcription‑quantitative polymerase chain reaction was used to analyze microRNA‑148a expression levels, MTT and flow cytometry assays were used to examine cytotoxicity and apoptosis, respectively. The gap‑associated proteins were quantified using western blotting. The expression of microRNA‑148a was significantly increased in osteoporosis rat following ovariectomy...
April 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29620243/knockdown-of-peroxiredoxin-v-increases-glutamate%C3%A2-induced-apoptosis-in-ht22-hippocampal-neuron-cells
#10
Gui-Nan Shen, Lei Liu, Li Feng, Yu Jin, Mei-Hua Jin, Ying-Hao Han, Cheng-Hao Jin, Yong-Zhe Jin, Dong-Soek Lee, Tae Ho Kwon, Yu-Dong Cui, Hu-Nan Sun
High concentrations of glutamate may mediate neuronal cell apoptosis by increasing intracellular reactive oxygen species (ROS) levels. Peroxiredoxin V (Prx V), a member of the Prx family, serves crucial roles in protecting cells from oxidative stress. The present study investigated the regulatory effect of Prx V on glutamate‑induced effects on viability and apoptosis in HT22 cells. Western blotting was used for protein expression analysis and Annexin V/PI staining and flow cytometry for determination of apoptosis...
March 29, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#11
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29619193/sensing-iron-availability-via-the-fragile-4fe-4s-cluster-of-the-bacterial-transcriptional-repressor-rira
#12
Ma Teresa Pellicer Martinez, Ana Bermejo Martinez, Jason C Crack, John D Holmes, Dimitri A Svistunenko, Andrew W B Johnston, Myles R Cheesman, Jonathan D Todd, Nick E Le Brun
Rhizobial iron regulator A (RirA) is a global regulator of iron homeostasis in many nitrogen-fixing Rhizobia and related species of α-proteobacteria. It belongs to the widespread Rrf2 super-family of transcriptional regulators and features three conserved Cys residues that characterise the binding of an iron-sulfur cluster in other Rrf2 family regulators. Here we report biophysical studies demonstrating that RirA contains a [4Fe-4S] cluster, and that this form of the protein binds RirA-regulated DNA, consistent with its function as a repressor of expression of many genes involved in iron uptake...
December 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29619013/phosphorylation-of-the-bacillus-subtilis-replication-controller-yaba-plays-a-role-in-regulation-of-sporulation-and-biofilm-formation
#13
Tránsito García García, Magali Ventroux, Abderahmane Derouiche, Vladimir Bidnenko, Sara Correia Santos, Céline Henry, Ivan Mijakovic, Marie-Françoise Noirot-Gros, Sandrine Poncet
Bacillus subtilis cells can adopt different life-styles in response to various environmental cues, including planktonic cells during vegetative growth, sessile cells during biofilm formation and sporulation. While switching life-styles, bacteria must coordinate the progression of their cell cycle with their physiological status. Our current understanding of the regulatory pathways controlling the decision-making processes and triggering developmental switches highlights a key role of protein phosphorylation...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29618720/anti-tnf-and-thiopurine-therapy-in-pregnant-ibd-patients-does-not-significantly-alter-a-panel-of-b-cell-and-t-cell-subsets-in-1-year-old-infants
#14
Michael G Kattah, Jeffrey M Milush, Trevor Burt, Robert P McCabe, Michael I Whang, Averil Ma, Uma Mahadevan
OBJECTIVES: Infants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared to unexposed infants. We hypothesized that this increased risk of infection is due to abnormal development of the newborn immune system. METHODS: We immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD...
April 3, 2018: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/29618492/autophagy-regulates-testosterone-synthesis-by-facilitating-cholesterol-uptake-in-leydig-cells
#15
Fengyi Gao, Guoping Li, Chao Liu, Hui Gao, Hao Wang, Weixiao Liu, Min Chen, Yongliang Shang, Lina Wang, Jian Shi, Wenlong Xia, Jianwei Jiao, Fei Gao, Jian Li, Liang Chen, Wei Li
Testosterone is indispensable for sexual development and maintaining male characteristics, and deficiency of this hormone results in primary or late-onset hypogonadism (LOH). Testosterone is primarily produced in Leydig cells, where autophagy has been reported to be extremely active. However, the functional role of autophagy in testosterone synthesis remains unknown. In this study, we show that steroidogenic cell-specific disruption of autophagy influenced the sexual behavior of aging male mice because of a reduction in serum testosterone, which is similar to the symptoms of LOH...
April 4, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29618088/cell-wall-synthesis-and-ribosome-maturation-are-co-regulated-by-an-rna-switch-in-mycobacterium-tuberculosis
#16
Stefan Schwenk, Alexandra Moores, Irene Nobeli, Timothy D McHugh, Kristine B Arnvig
The success of Mycobacterium tuberculosis relies on the ability to switch between active growth and non-replicating persistence, associated with latent TB infection. Resuscitation promoting factors (Rpfs) are essential for the transition between these states. Rpf expression is tightly regulated as these enzymes are able to degrade the cell wall, and hence potentially lethal to the bacterium itself. We have identified a regulatory element in the 5' untranslated region (UTR) of rpfB. We demonstrate that this element is a transcriptionally regulated RNA switch/riboswitch candidate, which appears to be restricted to pathogenic mycobacteria, suggesting a role in virulence...
March 29, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29617360/toxicological-and-pharmacological-assessment-of-agen1884-a-novel-human-igg1-anti-ctla-4-antibody
#17
Randi B Gombos, Ana Gonzalez, Mariana Manrique, Dhan Chand, David Savitsky, Benjamin Morin, Ekaterina Breous-Nystrom, Christopher Dupont, Rebecca A Ward, Cornelia Mundt, Benjamin Duckless, Hao Tang, Mark A Findeis, Andrea Schuster, Jeremy D Waight, Dennis Underwood, Christopher Clarke, Gerd Ritter, Taha Merghoub, David Schaer, Jedd D Wolchok, Marc van Dijk, Jennifer S Buell, Jean-Marie Cuillerot, Robert Stein, Elise E Drouin, Nicholas S Wilson
CTLA-4 and CD28 exemplify a co-inhibitory and co-stimulatory signaling axis that dynamically sculpts the interaction of antigen-specific T cells with antigen-presenting cells. Anti-CTLA-4 antibodies enhance tumor-specific immunity through a variety of mechanisms including: blockade of CD80 or CD86 binding to CTLA-4, repressing regulatory T cell function and selective elimination of intratumoral regulatory T cells via an Fcγ receptor-dependent mechanism. AGEN1884 is a novel IgG1 antibody targeting CTLA-4. It potently enhanced antigen-specific T cell responsiveness that could be potentiated in combination with other immunomodulatory antibodies...
2018: PloS One
https://www.readbyqxmd.com/read/29617057/antigen-specific-helios-neuropilin-1-tregs-induce-apoptosis-of-autoreactive-b-cells-via-pd-l1
#18
Janine Gotot, Ermanila Dhana, Hideo Yagita, Romina Kaiser, Isis Ludwig-Portugall, Christian Kurts
Regulatory T cells (Tregs) maintain self-tolerance and prevent autoimmunity by controlling autoreactive T cells. We recently demonstrated in vivo that Tregs can directly suppress auto-reactive B cells via programmed death ligand 1 (PD-L1) that ligated PD-1 on B cells and caused them to undergo apoptosis. Here we asked whether this mechanism is utilized by thymus-derived natural Tregs and/or by peripheral lymphoid tissue-induced Tregs. We first demonstrated that antigen-specific PD-L1-expressing Tregs were induced in the draining lymph node (LN) of autoantigen-expressing tissue and characterized them by their lack of the transcription factor Helios and of the surface marker Neuropilin-1 (Nrp-1)...
April 4, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29615467/late-neuroprogenitors-contribute-to-normal-retinal-vascular-development-in-a-hif2a-dependent-manner
#19
Enrico Cristante, Sidath E Liyanage, Robert D Sampson, Aikaterini Kalargyrou, Giulia De Rossi, Matteo Rizzi, Justin Hoke, Joana Ribeiro, Ryea N Maswood, Yanai Duran, Takaaki Matsuki, Nozie Aghaizu, Ulrich F Luhmann, Alexander J Smith, Robin R Ali, James W B Bainbridge
In the adult central nervous system, endothelial and neuronal cells engage in tight cross-talk as key components of the so-called neurovascular unit. Impairment of their critical relationship adversely affects tissue homeostasis, as observed in neurodegenerative conditions including Alzheimer's and Parkinson's disease. In development, the influence of neuroprogenitor cells on angiogenesis is poorly understood. Here, we show that these cells interact intimately with the growing retinal vascular network, and we identify a novel regulatory mechanism of vasculature development mediated by hypoxia-inducible factor 2a ( Hif2a )...
April 3, 2018: Development
https://www.readbyqxmd.com/read/29615416/the-drosophila-tgf-beta-activin-like-ligands-dawdle-and-myoglianin-appear-to-modulate-adult-lifespan-through-regulation-of-26s-proteasome-function-in-adult-muscle
#20
Shaughna Langerak, Myung-Jun Kim, Hannah Lamberg, Michael Godinez, Mackenzie Main, Lindsey Winslow, Michael B O'Connor, Changqi C Zhu
The Drosophila Activin signaling pathway employs at least three separate ligands, Activin-β (Actβ), Dawdle (Daw), and Myoglianin (Myo), to regulate several general aspects of fruit fly larval development including cell proliferation, neuronal remodeling, and metabolism. Here we provide experimental evidence indicating that both Daw and Myo are anti-ageing factors in adult fruit flies. Knockdown of Myo or Daw in adult fruit flies reduced mean lifespan, while overexpression of either ligand in adult muscle tissues but not in adipose tissues enhanced mean lifespan...
April 3, 2018: Biology Open
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