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https://www.readbyqxmd.com/read/28817403/primary-bone-lymphoma-exhibits-a-favorable-prognosis-and-distinct-gene-expression-signatures-resembling-diffuse-large-b-cell-lymphoma-derived-from-centrocytes-in-the-germinal-center
#1
Xin Li, Zijun Y Xu-Monette, Shuhua Yi, Bouthaina S Dabaja, Ganiraju C Manyam, Jason Westin, Nathan Fowler, Roberto N Miranda, Mingzhi Zhang, Judith A Ferry, L Jeffrey Medeiros, Nancy L Harris, Ken H Young
Primary bone (PB) diffuse large B-cell lymphoma (DLBCL) is rare and has a favorable prognosis, but the underlying biological mechanisms remain unknown. In this study we analyzed the clinicopathologic features of 160 patients with PB-DLBCL in comparison with 499 nonosseous DLBCL. Compared with patients with nonosseous DLBCL and secondary involvement of bone by DLBCL, PB-DLBCL patients less frequently had elderly age, B-symptoms, elevated serum lactate dehydrogenase levels, and high International Prognostic Index at diagnosis, more frequently had germinal center (GC) subtype (approximately 90%) and complete remission, and had significantly better survival...
August 16, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28810929/the-impact-of-age-and-gut-microbiota-on-th17-and-tfh-cells-in-k-bxn-autoimmune-arthritis
#2
Fei Teng, Krysta M Felix, C Pierce Bradley, Debdut Naskar, Heqing Ma, Walid A Raslan, Hsin-Jung Joyce Wu
BACKGROUND: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. METHODS: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis...
August 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28807996/klhl6-deficiency-impairs-transitional-b-cell-survival-and-differentiation
#3
Barbara Bertocci, Damiana Lecoeuche, Delphine Sterlin, Julius Kühn, Baptiste Gaillard, Annie De Smet, Frederique Lembo, Christine Bole-Feysot, Nicolas Cagnard, Tatiana Fadeev, Auriel Dahan, Jean-Claude Weill, Claude-Agnès Reynaud
Klhl6 belongs to the KLHL gene family, which is composed of an N-terminal BTB-POZ domain and four to six Kelch motifs in tandem. Several of these proteins function as adaptors of the Cullin3 E3 ubiquitin ligase complex. In this article, we report that Klhl6 deficiency induces, as previously described, a 2-fold reduction in mature B cells. However, we find that this deficit is centered on the inability of transitional type 1 B cells to survive and to progress toward the transitional type 2 B cell stage, whereas cells that have passed this step generate normal germinal centers (GCs) upon a T-dependent immune challenge...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28802258/human-blood-tfr-cells-are-indicators-of-ongoing-humoral-activity-not-fully-licensed-with-suppressive-function
#4
Valter R Fonseca, Ana Agua-Doce, Ana Raquel Maceiras, Wim Pierson, Filipa Ribeiro, Vasco C Romão, Ana Rita Pires, Susana Lopes da Silva, João Eurico Fonseca, Ana E Sousa, Michelle A Linterman, Luis Graca
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells and are crucial for the generation of high-affinity antibodies. Although the biology of human circulating and tissue Tfh cells has been established, the relationship between blood and tissue Tfr cells defined as CXCR5(+)Foxp3(+) T cells remains elusive. We found that blood Tfr cells are increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially in patients with high autoantibody titers, as well as in healthy individuals upon influenza vaccination...
August 11, 2017: Science Immunology
https://www.readbyqxmd.com/read/28800008/epstein-barr-virus-infection-can-be-a-secondary-event-in-b-cell-lymphomas-a-review-of-338-cases-and-a-novel-finding-of-zonal-eber-tumor-cells-showing-features-of-progression-from-underlying-ebv-negative-lymphoma
#5
Ira J Miller
Cases of B-cell lymphoma over an 8-year interval with diagnosis of EBER positivity were retrieved from archives and reviewed for classification and pattern of Epstein Barr Virus (EBV) expression. Of 46 cases that were EBV early RNA (EBER)+ by in situ hybridization staining, 7 had nonuniform staining among the neoplastic cells. Four of those cases showed a uniform admixture of EBER+ and EBER- tumor cells, compatible with the prevailing theory of episomal EBV loss with cell replication. Three cases of lymphomas showed a partial and zonal pattern and other features suggest that EBV infection occurred after the lymphoma was already established...
August 9, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28798767/in-arabidopsis-thaliana-cadmium-impact-on-the-growth-of-primary-root-by-altering-scr-expression-and-auxin-cytokinin-cross-talk
#6
Leonardo Bruno, Marianna Pacenza, Ivano Forgione, Liam R Lamerton, Maria Greco, Adriana Chiappetta, Maria B Bitonti
Cadmium is one of the most widespread pollutant in both terrestrial and marine environment, and its inhibitory effect on plant growth has been largely demonstrated. However, the molecular mechanisms underlying Cd toxicity in plant and mainly in root, as the first organ sensing soil heavy metals, need to be better investigated. To this aim, in the present work we analyzed the growth and the organization of Arabidopsis thaliana primary root in seedlings exposed to Cd (25 and 50 μM) for 8 days starting from germination...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28796588/obinutuzumab-or-rituximab-plus-cyclophosphamide-doxorubicin-vincristine-and-prednisone-in-previously-untreated-diffuse-large-b-cell-lymphoma
#7
Umberto Vitolo, Marek Trněný, David Belada, John M Burke, Angelo Michele Carella, Neil Chua, Pau Abrisqueta, Judit Demeter, Ian Flinn, Xiaonan Hong, Won Seog Kim, Antonio Pinto, Yuan-Kai Shi, Yoichi Tatsumi, Mikkel Z Oestergaard, Michael Wenger, Günter Fingerle-Rowson, Olivier Catalani, Tina Nielsen, Maurizio Martelli, Laurie H Sehn
Purpose Rituximab (R) plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy is the standard of care in previously untreated diffuse large B-cell lymphoma (DLBCL). Obinutuzumab (G) is a glycoengineered, type II, anti-CD20 monoclonal antibody. GOYA was a randomized phase III study that compared G-CHOP with R-CHOP in patients with previously untreated advanced-stage DLBCL. Methods Patients (N = 1,418) were randomly assigned to receive eight 21-day cycles of G (n = 706) or R (n = 712), plus six or eight cycles of CHOP...
August 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28783670/low-cd21-expression-defines-a-population-of-recent-germinal-center-graduates-primed-for-plasma-cell-differentiation
#8
Denise Lau, Linda Yu-Ling Lan, Sarah F Andrews, Carole Henry, Karla Thatcher Rojas, Karlynn E Neu, Min Huang, Yunping Huang, Brandon DeKosky, Anna-Karin E Palm, Gregory C Ippolito, George Georgiou, Patrick C Wilson
In this study, we report that antigen-specific CD19(+)CD27(+)CD21(lo) (CD21(lo)) B cells are transiently induced 14 to 28 days after immunization, at the time germinal centers (GCs) peak. Although clonally related to memory B cells and plasmablasts, CD21(lo) cells form distinct clades within phylogenetic trees based on accumulated variable gene mutations, supporting exit from active GCs. CD21(lo) cells express a transcriptional program, suggesting that they are primed for plasma cell differentiation and are refractory to GC differentiation, although they do not spontaneously secrete antibody...
January 27, 2017: Science Immunology
https://www.readbyqxmd.com/read/28775174/comparison-of-protein-based-cell-of-origin-classification-to-the-lymph2cx-rna-assay-in-a-cohort-of-diffuse-large-b-cell-lymphomas-in-malaysia
#9
Kean-Chang Phang, Ariz Akhter, Nur Maya Sabrina Tizen, Faridah Abd Rahman, Raja Zahratul Azma, Ghaleb Elyamany, Meer-Taher Shabani-Rad, Noraidah Masir, Adnan Mansoor
AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world...
August 3, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28770576/transformed-waldenstr%C3%A3-m-macroglobulinaemia-clinical-presentation-and-outcome-a-multi-institutional-retrospective-study-of-77-cases-from-the-french-innovative-leukemia-organization-filo
#10
Eric Durot, Cécile Tomowiak, Anne-Sophie Michallet, Jehan Dupuis, Bénédicte Hivert, Stéphane Leprêtre, Elise Toussaint, Sophie Godet, Fatiha Merabet, Eric Van Den Neste, Sarah Ivanoff, Xavier Roussel, Jean-Marc Zini, Caroline Regny, Richard Lemal, Laurent Sutton, Aurore Perrot, Katell Le Dû, Lukshe Kanagaratnam, Pierre Morel, Véronique Leblond, Alain Delmer
Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy-proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement...
August 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28768709/co-stimulatory-function-in-primary-germinal-center-responses-cd40-and-b7-are-required-on-distinct-antigen-presenting-cells
#11
Masashi Watanabe, Chiharu Fujihara, Andrea J Radtke, Y Jeffrey Chiang, Sumeena Bhatia, Ronald N Germain, Richard J Hodes
T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production...
August 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28767707/murine-gammaherpesvirus-m2-antigen-modulates-splenic-b-cell-activation-and-terminal-differentiation-in-vivo
#12
Shariya Terrell, Samuel H Speck
Murine gammaherpesvirus 68 (MHV68) infection of laboratory strains of mice has provided a tractable small animal model for dissecting gammaherpesvirus pathogenesis. The MHV68 latency associated antigen M2 promotes viral latency establishment in germinal center (GC) B cells and plays an important role in virus infection of plasma cells (PCs), which is linked to virus reactivation. More recently, M2 has been highlighted as a potent immunomodulatory molecule capable of hindering both cell-mediated and humoral immunity to MHV68 infection and subsequent challenges...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28762497/t-cell-dependent-antigen-adjuvanted-with-dotap-cpg-b-but-not-dotap-cpg-a-induces-robust-germinal-center-responses-and-high-affinity-antibodies-in-mice
#13
Munir Akkaya, Billur Akkaya, Patrick W Sheehan, Pietro Miozzo, Mirna Pena, Chen-Feng Qi, Javier Manzella-Lapeira, Silvia Bolland, Susan K Pierce
The development of vaccines for infectious diseases for which we currently have none, including HIV, will likely require the use of adjuvants that strongly promote germinal center responses and somatic hypermutation to produce broadly neutralizing antibodies. Here we compared the outcome of immunization with the T-cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG) adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or conjugated with the cationic lipid carrier, DOTAP...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28760903/tetrazole-based-trans-translation-inhibitors-kill-bacillus-anthracis-spores-to-protect-host-cells
#14
John N Alumasa, Tyler D P Goralski, Kenneth C Keiler
Bacillus anthracis, the causative agent of anthrax, remains a significant threat to humans, including potential use in bioterrorism and biowarfare. The capacity to engineer strains with increased pathogenicity coupled with the ease of disseminating lethal doses of B. anthracis spores makes it necessary to identify chemical agents that target and kill spores. Here, we demonstrate that a tetrazole-based trans-translation inhibitor, KKL-55, is bactericidal against vegetative cells of B. anthracis in culture. Using a fluorescent analog, we show that this class of compounds co-localizes with developing endospores and bind purified spores in vitro KKL-55 was effective against spores at concentrations close to its MIC for vegetative cells...
July 31, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28760610/macrophage-derived-insulin-like-growth-factor-1-affects-influenza-vaccine-efficacy-through-the-regulation-of-immune-cell-homeostasis
#15
Il-Sub Yoon, Hyelim Park, Hye-Won Kwak, Yong Woo Jung, Jae-Hwan Nam
The level of antibody production induced by a vaccine involves a variety of host factors. One of these, insulin-like growth factor-1 (IGF-1), plays an important role in lymphocyte maturation and antibody expression. Here, we investigated the role of macrophage-derived IGF-1 in the induction of influenza vaccine-specific antibodies using macrophage-derived IGF-1 gene knockout (MIKO) mice. The titers of vaccine-specific total immunoglobulin G (IgG) and IgG1 after immunization were about two- to fourfold lower in MIKO mice than in WT mice...
July 28, 2017: Vaccine
https://www.readbyqxmd.com/read/28760529/discovery-of-a-novel-b-cell-lymphoma-6-bcl6-corepressor-interaction-inhibitor-by-utilizing-structure-based-drug-design
#16
Takeshi Yasui, Takeshi Yamamoto, Nozomu Sakai, Kouhei Asano, Takafumi Takai, Yayoi Yoshitomi, Melinda Davis, Terufumi Takagi, Kotaro Sakamoto, Satoshi Sogabe, Yusuke Kamada, Weston Lane, Gyorgy Snell, Masashi Iwata, Masayuki Goto, Hiroshi Inooka, Jun-Ichi Sakamoto, Yoshihisa Nakada, Yasuhiro Imaeda
B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits 1a and 2a, we identified a novel BCL6-corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC50=0...
September 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28756244/high-frequency-of-bob1-lo-t-follicular-helper-cells-in-florid-reactive-follicular-hyperplasia
#17
Hiroshi Matsumiya, Koji Kawata, Ryuta Kamekura, Chieko Tsubomatsu, Sumito Jitsukawa, Takamasa Asai, Syunsuke Akasaka, Motonari Kamei, Keiji Yamashita, Fumie Ito, Terufumi Kubo, Noriyuki Sato, Ken-Ichi Takano, Tetsuo Himi, Shingo Ichimiya
Florid reactive follicular hyperplasia (FRFH), which is characterized by large germinal centers (GCs) within normal lymphoid follicles, is often observed in benign lesions of lymph nodes and other tissues. Because of the histologic similarity of FRFH to tumorous lesions such as follicular lymphoma, careful pathological examination is required to evaluate such lesions; however, little is known about the mechanism underlying the development of FRFH. In this study, we investigated T follicular helper (Tfh) cells in hyperplastic tonsils of patients with obstructive sleep apnea syndrome (OSA), which frequently exhibits typical FRFH...
July 26, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28755339/indirect-somatic-embryogenesis-of-date-palm-using-juvenile-leaf-explants-and-low-2-4-d-concentration
#18
Lotfi Fki, Walid Kriaa, Ameni Nasri, Emna Baklouti, Olfa Chkir, Raja B Masmoudi, Alain Rival, Noureddine Drira
This chapter describes an efficient protocol for large-scale micropropagation of date palm. Somatic embryo-derived plants are regenerated from highly proliferating suspension cultures. Friable embryogenic callus is initiated from juvenile leaves using slightly modified Murashige and Skoog (MS) medium supplemented with 0.1 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D). Suspension cultures consisting of proembryonic masses are established from highly competent callus for somatic embryogenesis using half-strength MS medium enriched with 0...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28749570/hepatocyte-derived-exosomes-promote-t-follicular-regulatory-cell-expansion-during-hcv-infection
#19
Dustin A Cobb, Lucy Golden-Mason, Hugo R Rosen, Young S Hahn
Hepatitis C virus (HCV) is a global health concern that can cause severe liver disease such as cirrhosis and hepatocellular carcinoma. Control of HCV requires vigorous T cell responses, yet CD4(+) T cells in chronic HCV patients are dysfunctional. T follicular regulatory (Tfr) cells are a subset of regulatory T cells that suppress T follicular helper (Tfh) cells and the generation of high affinity antibody-producing B cells. In this study, we examined the accumulation of Tfr cells in the liver compartment during chronic HCV infection and defined the cellular and molecular mechanisms underlying their expansion...
July 27, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28748530/il-6-promotes-cd4-t-cell-and-b-cell-activation-during-plasmodium-infection
#20
Ismail Sebina, Lily G Fogg, Kylie R James, Megan S F Soon, Jasmin Akter, Bryce S Thomas, Geoffrey R Hill, Christian R Engwerda, Ashraful Haque
AIMS: Humoral immunity develops in the spleen during blood-stage Plasmodium infection. This elicits parasite-specific IgM and IgG, which control parasites and protect against malaria. Studies in mice have elucidated cells and molecules driving humoral immunity to Plasmodium, including CD4(+) T-cells, B-cells, interleukin (IL)-21 and ICOS. IL-6, a cytokine readily detected in Plasmodium-infected mice and humans, is recognized in other systems as a driver of humoral immunity. Here, we examined the effect of infection-induced IL-6 on humoral immunity to Plasmodium...
July 27, 2017: Parasite Immunology
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