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https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#1
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908305/abatacept-treatment-of-patients-with-primary-sj%C3%A3-gren-s-syndrome-results-in-a-decrease-of-germinal-centres-in-salivary-gland-tissue
#2
Erlin A Haacke, Bert van der Vegt, Petra M Meiners, Arjan Vissink, Fred K L Spijkervet, Hendrika Bootsma, Frans G M Kroese
OBJECTIVES: The aim of this study was to assess the histopathological changes in parotid gland tissue of primary Sjögren's syndrome (pSS) patients treated with abatacept. METHODS: In all 15 pSS patients included in the open-label Active Sjögren Abatacept Pilot (ASAP, 8 abatacept infusions) study parotid gland biopsies were taken before treatment and at 24 weeks of follow up. Biopsies were analysed for pSS-related histopathological features and placed in context of clini- cal responsiveness as assessed with EULAR Sjögren's syndrome disease activity index (ESSDAI)...
November 12, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27907250/the-transcriptional-co-activator-bob1-is-associated-with-pathologic-b-cell-responses-in-autoimmune-tissue-inflammation
#3
Maria J Levels, Melissa N Van Tok, Tineke Cantaert, Juan D Cañete, Frans G M Kroese, Kristine Germar, Hergen Spits, Dominique L P Baeten, Nataliya G Yeremenko
OBJECTIVE: The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. In this study we aimed to identify molecular switches controlling pathological B cell responses in rheumatoid arthritis (RA). METHODS: Candidate molecules were identified by gene expression profiling of RA synovitis and validated by qPCR and immunohistochemistry. B cell-specific expression was confirmed by immunofluorescence, immunoblotting and flow cytometry...
December 1, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27907212/diffuse-large-b-cell-lymphoma-cell-line-u-2946-model-for-mcl1-inhibitor-testing
#4
Hilmar Quentmeier, Hans G Drexler, Vivien Hauer, Roderick A F MacLeod, Claudia Pommerenke, Cord C Uphoff, Margarete Zaborski, Mattias Berglund, Gunilla Enblad, Rose-Marie Amini
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8;14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n)...
2016: PloS One
https://www.readbyqxmd.com/read/27906827/cross-talk-between-t-and-b-cells-in-the-germinal-center-following-transplantation
#5
Jean Kwun, Miriam Manook, Eugenia Page, Christopher Burghuber, Jungjoo Hong, Stuart J Knechtle
Cross-talk between B and T cells in transplantation is increasingly recognized as being important in the alloimmune response. T cell activation of B cells occurs by a 3-stage pathway, culminating with costimulation signals. We review the distinct T cell subtypes required for B cell activation, and discuss the formation of the Germinal Center (GC) after transplantation, with particular reference to the repopulation of the GC following depletional induction, and the subsequent effect of immunosuppressive manipulation of T-B cell interactions...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27904766/the-role-of-pim1-in-the-ibrutinib-resistant-abc-subtype-of-diffuse-large-b-cell-lymphoma
#6
Hsu-Ping Kuo, Scott A Ezell, Sidney Hsieh, Karl J Schweighofer, Leo Wk Cheung, Shiquan Wu, Mutiah Apatira, Mint Sirisawad, Karl Eckert, Yu Liang, Jeff Hsu, Chun-Te Chen, Darrin Beaupre, Betty Y Chang
Diffuse large B cell lymphoma (DLBCL) is a heterogeneous lymphoma and the most common subtype of non-Hodgkin lymphoma, accounting for roughly 30% of newly diagnosed cases in the United States. DLBCL can be separated into the activated B cell-like (ABC) and germinal center B cell-like (GCB) subtypes, with distinct gene expression profiles, oncogenic aberrations, and clinical outcomes. ABC-DLBCL is characterized by chronically active B-cell receptor (BCR) signaling that can be modulated by Bruton's tyrosine kinase (BTK) activity...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27902338/recombinant-rabies-virus-expressing-il-21-enhances-immunogenicity-through-activation-of-t-follicular-helper-cells-and-germinal-center-b-cells
#7
Yajing Zhang, Ming Zhou, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Huanchun Chen, Zhen F Fu, Ling Zhao
Previous studies have demonstrated that the lack of interleukin-21 (IL-21) signaling could affect specific antibody induction after rabies vaccination. Here, to further investigate the overexpression of IL-21 on the immunogenicity of rabies virus (RABV), a recombinant RABV expressing murine IL-21, designated as LBNSE-IL21, was constructed and evaluated in a mouse model. It was found that mice immunized with LBNSE-IL21 could substantially increase the number of T follicular helper (Tfh) cells and germinal center (GC) B cells but did not enhance dendritic cell (DC) activation...
October 25, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27897259/artemisinin-analogue-sm934-attenuate-collagen-induced-arthritis-by-suppressing-t-follicular-helper-cells-and-t-helper-17-cells
#8
Ze-Min Lin, Xiao-Qian Yang, Feng-Hua Zhu, Shi-Jun He, Wei Tang, Jian-Ping Zuo
SM934 is an artemisinin analogue with immunosuppressive properties and potent therapeutic activity against lupus-like diseases in autoimmune mice. In this report, the therapeutic efficacy and underlying mechanisms of SM934 on rheumatoid arthritis (RA) was investigated using collagen-induced arthritis (CIA) in DBA/1J mice. We demonstrated that SM934 treatment alleviate the severity of arthritis in CIA mice with established manifestations. The therapeutic benefits were associated with ameliorated joint swelling and reduced extent of bone erosion and destruction...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#9
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895177/ox40-cooperates-with-icos-to-amplify-follicular-th-cell-development-and-germinal-center-reactions-during-infection
#10
Vikas Tahiliani, Tarun E Hutchinson, Georges Abboud, Michael Croft, Shahram Salek-Ardakani
Cognate interactions between T follicular helper (Tfh) cells and B cells are essential for promoting protective Ab responses. Whereas costimulatory receptors such as ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. In this study, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T/B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral Ags...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27891132/impact-of-chronic-hiv-siv-infection-on-t-follicular-helper-cell-subsets-and-germinal-center-homeostasis
#11
REVIEW
Stéphanie Graff-Dubois, Angeline Rouers, Arnaud Moris
The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-infected patients develop bNAbs that arise late in the course of infection, indicating probable Tfh and B cell dysfunctions in this context. Since the last few years, many studies have characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals and SIV-infected macaques...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27889171/antifungal-activity-of-%C3%AE-carbolines-on-penicillium-digitatum-and-botrytis-cinerea
#12
Gabriela M Olmedo, Luciana Cerioni, M Micaela González, Franco M Cabrerizo, Viviana A Rapisarda, Sabrina I Volentini
β-carbolines (βCs) are alkaloids widely distributed in nature that have demonstrated antimicrobial properties. Here, we tested in vitro six βCs against Penicillium digitatum and Botrytis cinerea, causal agents of postharvest diseases on fruit and vegetables. Full aromatic βCs (harmine, harmol, norharmane and harmane) exhibited a marked inhibitory effect on conidia germination at concentrations between 0.5 and 1 mM, while dihydro-βCs (harmalina and harmalol) only caused germination delay. Harmol showed the highest inhibitory effect on both fungal pathogens...
April 2017: Food Microbiology
https://www.readbyqxmd.com/read/27887763/composite-lymphoma-with-diffuse-large-b-cell-lymphoma-and-classical-hodgkin-lymphoma-components-a-case-report-and-review-of-the-literature
#13
Gaurav Goyal, Austin Huy Nguyen, Kayla Kendric, Gabriel C Caponetti
Composite lymphoma (CL) is an infrequently diagnosed entity in which two or more distinct types of lymphomas occur synchronously in the same organ or anatomical site. Most commonly, CLs are composed of two non-Hodgkin B-cell lymphomas. We present a case of a composite lymphoma with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS) and classical Hodgkin lymphoma (CHL) components involving the terminal ileum, colon and pericolic lymph nodes. Immunohistochemical evaluation for determination of cell of origin of the DLBCL-NOS component indicated a germinal center B-cell subtype...
November 5, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27883180/mitochondrial-reactive-oxygen-species-suppress-humoral-immune-response-through-reduction-of-cd19-expression-in-b-cells-in-mice
#14
Masato Ogura, Takeshi Inoue, Junko Yamaki, Miwako K Homma, Tomohiro Kurosaki, Yoshimi Homma
Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A (SDHA(Y215F) ) in B cells (bSDHA(Y215F) ). Splenic B cells in male, but not female, bSDHA(Y215F) mice produced three times more ROS than those in the control mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity maturation of IgG1 against T-cell-dependent antigens...
November 24, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27880897/direct-probing-of-germinal-center-responses-reveals-immunological-features-and-bottlenecks-for-neutralizing-antibody-responses-to-hiv-env-trimer
#15
Colin Havenar-Daughton, Diane G Carnathan, Alba Torrents de la Peña, Matthias Pauthner, Bryan Briney, Samantha M Reiss, Jennifer S Wood, Kirti Kaushik, Marit J van Gils, Sandy L Rosales, Patricia van der Woude, Michela Locci, Khoa M Le, Steven W de Taeye, Devin Sok, Ata Ur Rasheed Mohammed, Jessica Huang, Sanjeev Gumber, AnaPatricia Garcia, Sudhir P Kasturi, Bali Pulendran, John P Moore, Rafi Ahmed, Grégory Seumois, Dennis R Burton, Rogier W Sanders, Guido Silvestri, Shane Crotty
Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27880797/regulation-and-maintenance-of-an-adoptive-t-cell-dependent-memory-b-cell-pool
#16
Marie Anson, Inês Amado, Marie-Pierre Mailhé, Emmanuel Donnadieu, Sylvie Garcia, François Huetz, Antonio A Freitas
We investigated the ability of monoclonal B cells to restore primary and secondary T-cell dependent antibody responses in adoptive immune-deficient hosts. Priming induced B cell activation and expansion, AID expression, antibody production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell subsets that persisted in the lymphopenic environment by cell division. Upon secondary transfer and recall the IgM-IgG+ cells responded by the production of antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little IgG, but generated new B cells expressing germinal center markers...
2016: PloS One
https://www.readbyqxmd.com/read/27876630/disruptions-of-the-genes-involved-in-lysine-biosynthesis-iron-acquisition-and-secondary-metabolisms-affect-virulence-and-fitness-in-metarhizium-robertsii
#17
Bruno Giuliano Garisto Donzelli, B Gillian Turgeon, Donna M Gibson, Stuart B Krasnoff
Based on genomic analysis, polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) pathways account for biosynthesis of the majority of the secondary metabolites produced by the entomopathogenic fungus Metarhizium robertsii. To evaluate the contribution of these pathways to M. robertsii fitness and/or virulence, mutants deleted for mrpptA, the Sfp-type 4' phosphopantetheinyl transferase gene required for their activation were generated. ΔmrpptA strains were deficient in PKS and NRPS activity resulting in colonies lacking the typical green pigment that failed to produce the nonribosomal peptides destruxins, serinocylins, and the siderophores ferricrocin and metachelins, as well as the hybrid polyketide-peptides NG-39x that are all produced by the wild type (WT) M...
November 19, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/27873317/b-cell-activating-factor-signalling-pathway-is-associated-with-h-pylori-independence-in-gastric-malt-lymphoma-without-t-11-18-q21-q21
#18
Sung-Hsin Kuo, Hui-Jen Tsai, Chung-Wu Lin, Kun-Huei Yeh, Hsiao-Wei Lee, Ming-Feng Wei, Chia-Tung Shun, Ming-Shiang Wu, Ping-Ning Hsu, Li-Tzong Chen, Ann-Lii Cheng
We previously reported that activation of the B cell-activating factor (BAFF) pathway upregulates NF-κB and induces BCL3 and BCL10 nuclear translocation in H. pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (DLBCL [MALT]). However, the significance of BAFF expression in HP-independence of gastric low-grade MALT lymphomas (MALT lymphoma) without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied...
November 22, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27866903/emerging-concepts-in-t-follicular-helper-cell-responses-to-malaria
#19
REVIEW
Diana S Hansen, Nyamekye Obeng-Adjei, Ann Ly, Lisa J Ioannidis, Peter D Crompton
Antibody responses to malaria and candidate malaria vaccines are short-lived in children, leaving them susceptible to repeated malaria episodes. Because T follicular helper (TFH) cells provide critical help to B cells to generate long-lived antibody responses, they have become the focus of recent studies of Plasmodium-infected mice and humans. The emerging data converge on common themes, namely, that malaria-induced TH1 cytokines are associated with the activation of (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre-TFH cells that acquire Th1-like features (T-bet expression, IFN-γ production), which impede their differentiation into fully functional TFH cells, thus resulting in germinal center dysfunction and suboptimal antibody responses...
November 17, 2016: International Journal for Parasitology
https://www.readbyqxmd.com/read/27865860/human-regulatory-b-cells-control-tfh-response
#20
Achouak Achour, Quentin Simon, Audrey Mohr, Jean-François Séité, Pierre Youinou, Boutahar Bendaoud, Ibtissem Ghedira, Jacques-Olivier Pers, Christophe Jamin
BACKGROUND: Follicular helper T (Tfh) cells support the terminal B-cell differentiation. Human regulatory B (Breg) cells modulate cellular responses but their control of Tfh-dependent humoral immune responses is unknown. OBJECTIVE: To assess the role of Breg cells on Tfh development and function. METHODS: Human T cells were polyclonally stimulated in the presence of IL-12 and IL-21 to generate Tfh cells. They were co-cultured with B cells to induce their terminal differentiation...
November 16, 2016: Journal of Allergy and Clinical Immunology
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