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Germinal center

Vivek Kumar, Navneet Mittal, Yiwu Huang, Jasminka Balderracchi, Huo Xiang Zheng, Zujin Li, Yiqing Xu
Kimura's disease (KD) is a rare, benign disorder characterized by subcutaneous masses with regional lymph-node enlargement. It is considered to be due to chronic inflammation of unclear etiology. Most cases have been reported in young, 20-30-year-old men of Asian descent. The diagnosis of KD is based on pathological features and elevated immunoglobulin E levels. Characteristic pathological features include intact lymph-node architecture, florid germinal center hyperplasia, extensive eosinophilic infiltrates, and proliferation of postcapillary venules...
July 2018: Therapeutic Advances in Hematology
Markus M Xie, Alexander L Dent
Follicular helper T (Tfh) cells are necessary for germinal center (GC) formation and within the GC, provide key signals to B cells for their differentiation into plasmablasts and plasma cells that secrete high-affinity and isotype-switched antibody (Ab). A specialized subset of Foxp3+ T cells termed T follicular regulatory (Tfr) cells, also regulate the differentiation of Ab-secreting cells from the GC. Tfr-cell function in the GC is not well understood, however, the dominant paradigm currently is that Tfr cells repress excessive Tfh and GC B cell proliferation and help promote stringent selection of high-affinity B cells...
2018: Frontiers in Immunology
Sunglim Cho, Hyang-Mi Lee, I-Shing Yu, Youn Soo Choi, Hsi-Yuan Huang, Somaye Sadat Hashemifar, Ling-Li Lin, Mei-Chi Chen, Nikita D Afanasiev, Aly Azeem Khan, Shu-Wha Lin, Alexander Y Rudensky, Shane Crotty, Li-Fan Lu
Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146a and its paralog, miR-146b, in T cells increases Tfh cell numbers and enhanced GC reactions...
July 16, 2018: Nature Communications
Daria Radchenko, Ines Teichert, Stefanie Pöggeler, Ulrich Kück
The supramolecular striatin-interacting phosphatases and kinases (STRIPAK) complex is conserved from yeast to human and regulates a variety of key biological processes. In animals, this complex consists of the scaffold protein striatin, the protein phosphatase 2A (PP2A), and kinases, such as germinal center kinase III (GCKIII) and GCKIV family members, as well as other associated proteins. The STRIPAK complex was identified as a negative regulator of the Hippo pathway, a large eukaryotic signaling network with a core composed of a GCK and a nuclear dbf-2 related (NDR) kinase...
July 16, 2018: Genetics
Cynthia Louis, Devi Ngo, Damian B D'Silva, Jacinta Hansen, Louisa Phillipson, Helene Jousset, Patrizia Novello, David Segal, Kate E Lawlor, Christopher J Burns, Ian P Wicks
OBJECTIVE: The production of class-switched high-affinity autoantibodies derived from organised germinal centers (GC) is a hallmark of many autoimmune inflammatory diseases, including rheumatoid arthritis (RA). TANK-binding kinase 1 (TBK1) is a serine-threonine kinase involved in the maturation of GC T follicular B helper cells (TFH ) downstream of inducible T cell costimulator (ICOS) signalling. We therefore assessed the therapeutic potential of TBK1 inhibition using a small molecule inhibitor - known as WEHI-112 - in antibody dependent models of inflammatory arthritis...
July 15, 2018: Arthritis & Rheumatology
Alvaro Baeza Garcia, Edwin Siu, Tiffany Sun, Valerie Exler, Luis Brito, Armin Hekele, Gib Otten, Kevin Augustijn, Chris J Janse, Jeffrey B Ulmer, Jürgen Bernhagen, Erol Fikrig, Andrew Geall, Richard Bucala
Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-α, IL-12, and IFN-γ during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells...
July 13, 2018: Nature Communications
Wenqin Yue, Bin Liu, Lei Gao, Miaoxia He, Jianmin Wang, Weiping Zhang, Li Chen, Xiaoxia Hu, Lili Xu, Jianmin Yang
BACKGROUND: The pretreatment albumin to globulin ratio (AGR) has been used to predict survival in several types of tumors. However, whether AGR can predict outcomes in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. We evaluated the prognosis value of AGR in DLBCL patients. METHODS: We retrospectively analyzed the available serum biochemical results of 335 patients with newly diagnosed DLBCL before treatment. The AGR was calculated as: albumin (g/L)/globulin...
July 10, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Fiona Raso, Sara Sagadiev, Samuel Du, Emily Gage, Tanvi Arkatkar, Genita Metzler, Lynda M Stuart, Mark T Orr, David Rawlings, Shaun Jackson, Adam Lacy-Hulbert, Mridu Acharya
Germinal centers (GCs) are major sites of clonal B cell expansion and generation of long-lived, high-affinity antibody responses to pathogens. Signaling through toll-like receptors(TLRs) on B cells promotes many aspects of GC B cell responses, including affinity-maturation, class-switching and differentiation into long-lived memory and plasma cells. A major challenge for effective vaccination is identifying strategies to specifically promote GC B cell responses. Here we have identified a mechanism of regulation of GC B cell TLR signaling, mediated by αv integrins and non-canonical autophagy...
July 12, 2018: Journal of Clinical Investigation
Mary K McCarthy, Bennett J Davenport, Glennys V Reynoso, Erin D Lucas, Nicholas A May, Susan A Elmore, Beth A Tamburini, Heather D Hickman, Thomas E Morrison
Chikungunya virus (CHIKV) causes acute and chronic rheumatologic disease. Pathogenic CHIKV strains persist in joints of immunocompetent mice, while the attenuated CHIKV strain 181/25 is cleared by adaptive immunity. We analyzed the draining lymph node (dLN) to define events in lymphoid tissue that may contribute to CHIKV persistence or clearance. Acute 181/25 infection resulted in dLN enlargement and germinal center (GC) formation, while the dLN of mice infected with pathogenic CHIKV became highly disorganized and depleted of lymphocytes...
July 12, 2018: JCI Insight
Phillip P Domeier, Sathi Babu Chodisetti, Stephanie L Schell, Yuka Imamura Kawasawa, Melinda J Fasnacht, Chetna Soni, Ziaur S M Rahman
Type 1 interferon (T1IFN) signaling promotes inflammation and lupus pathology, but its role in autoreactive B cell development in the antibody-forming cell (AFC) and germinal center (GC) pathways is unclear. Using a lupus model that allows for focused study of the AFC and GC responses, we show that T1IFN signaling is crucial for autoreactive B cell development in the AFC and GC pathways. Through bone marrow chimeras, DNA-reactive B cell transfer, and GC-specific Cre mice, we confirm that IFNαR signaling in B cells promotes autoreactive B cell development into both pathways...
July 10, 2018: Cell Reports
Zijian Liu, Jingshu Meng, Xiaoqian Li, Fang Zhu, Tao Liu, Gang Wu, Liling Zhang
There is a significant difference in prognosis between the germinal center B-cell (GCB) and activated B-cell (ABC) subtypes of diffuse large B-cell lymphoma (DLBCL). However, the signaling pathways and driver genes involved in these disparate subtypes are ambiguous. This study integrated three cohort profile datasets, including 250 GCB samples and 250 ABC samples, to elucidate potential candidate hub genes and key pathways involved in these two subtypes. Differentially expressed genes (DEGs) were identified...
2018: BioMed Research International
Maryam Seifi Kalhor, Sasan Aliniaeifard, Mehdi Seif, Elahe Javadi Asayesh, Françoise Bernard, Batool Hassani, Tao Li
Gamma-Amino Butyric Acid (GABA) is a substantial component of the free amino acid pool with low concentration in plant tissues. Enhanced GABA content occurs during plant growth and developmental processes like seed germination. GABA level, basically, alters in response to many endogenous and exogenous stimuli. In the current study, GABA effects were studied on germination, photosynthetic performance and oxidative damages in salt-exposed lettuce plants. Three NaCl (0, 40 and 80 mM) and two GABA (0 and 25 μM) concentrations were applied on lettuce during two different developmental (seed germination and seedlings growth) stages...
July 3, 2018: Plant Physiology and Biochemistry: PPB
Mengmeng Zhang, Yongxia Wu, David Bastian, Supinya Iamsawat, Jinsam Chang, Anusara Daenthanasanmak, Hung D Nguyen, Steven Schutt, Min Dai, Fangping Chen, Woong-Kyung Suh, Xue-Zhong Yu
The incidence of chronic graft-versus-host disease (cGVHD) is on the rise and still the major cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (HCT). Both donor T and B cells contribute to the pathogenesis of cGVHD. Inducible T-cell co-stimulator (ICOS), a potent co-stimulatory receptor, plays a key role in T-cell activation and differentiation. Yet, how ICOS regulates the development of cGVHD is not well understood. Here, we investigated the role of ICOS in cGVHD pathogenesis using mice with germline or regulatory T cell (Treg)-specific ICOS deficiency...
2018: Frontiers in Immunology
Ana Martínez-Riaño, Elena R Bovolenta, Pilar Mendoza, Clara L Oeste, María Jesús Martín-Bermejo, Paola Bovolenta, Martin Turner, Nuria Martínez-Martín, Balbino Alarcón
Successful vaccines rely on activating a functional humoral response that results from promoting a proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells that need to acquire antigens and to present them to cognate CD4 T cells. Here, we report that follicular B cells can phagocytose large antigen-coated particles, a process thought to be exclusive of specialized antigen-presenting cells such as macrophages and dendritic cells. We show that antigen phagocytosis by B cells is BCR-driven and mechanistically dependent on the GTPase RhoG...
July 9, 2018: EMBO Reports
Taiping Liu, Xiangyun Cheng, Yan Ding, Feng Zhu, Yong Fu, Xiaohong Peng, Wenyue Xu
BACKGROUND: T follicular helper (TFH) cells are fundamental for the development of humoral immunity. In our previous study, we found that PD-1 deficiency substantially promoted the expansion of Plasmodium-specific TFH cells and enhanced the humoral immunity of ITV (infection treatment vaccine)-immunized mice. However, the underlying mechanism by which PD-1 signaling modulates TFH cells activation remains unclear. METHODS: Mice were immunized with the ITV following the standard procedures...
July 6, 2018: Parasites & Vectors
Yi-Che ChangChien, Ilona Kovács, Zoltán Hargitai, László Magyar
INTRODUCTION: Paratesticular fibrous pseudotumor (PFP) represents a benign tumor-like lesion confined to intrascrotal, paratesticular areas. Due to its rarity, only less than 200 cases have been reported to date, of which both pathogenesis and clinical management are little understood. Recently, PFP has been postulated to be among the spectrum of so-called immunoglobulin G4-related diseases (IgG4-RD). Here we describe a case of PFP focusing on the clinical, morphological features and the utility of immunohistochemistry to support the theory that PFP might be a potential member of IgG4-RD family...
May 2018: Annals of Clinical and Laboratory Science
Keishi Makino, Hideo Nakamura, Naoki Shinojima, Jun-Ichiro Kuroda, Shigetoshi Yano, Yoshiki Mikami, Akitake Mukasa
PURPOSE: Primary central nervous system diffuse large B-cell lymphoma (CNS-DLBCL) is a distinct clinicopathological entity with a poor prognosis. Concurrent MYC and BCL2 overexpression predicts inferior prognosis in systemic DLBCL, although their prognostic significance remains unclear in primary CNS-DLBCL. METHODS: Pretreatment diagnostic biopsy samples were retrospectively evaluated for 79 patients with primary CNS-DLBCL who were treated between January 2001 and December 2017...
July 2, 2018: Journal of Neuro-oncology
Thomas Yssing Michaelsen, Julia Richter, Rasmus Froberg Brøndum, Wolfram Klapper, Hans Erik Johnsen, Mads Albertsen, Karen Dybkær, Martin Bøgsted
Gene expression profiling (GEP) by microarrays of diffuse large B-cell lymphoma (DLBCL) has enabled the categorization of DLBCL into activated B-cell-like and germinal center B-cell-like subclasses. However, as this does not fully embrace the great diversity of B-cell subtypes, we recently developed a gene expression assay for B-cell-associated gene signature (BAGS) classification. To facilitate quick and easy-to-use BAGS profiling, we developed in this study the NanoString-based BAGS2Clinic assay. Microarray data from 4 different cohorts (n = 970) were used to select genes and train the assay...
July 10, 2018: Blood Advances
Hee Young Na, Young A Kim, Cheol Lee, Ji-Young Choe, Seon Ah Shin, Jung-Weon Shim, Soo Kee Min, Hyun-Jung Kim, Jae Ho Han, Ji Eun Kim
Follicular lymphoma (FL) occurs primarily in the gastrointestinal tract, with the stomach being one of the rarest sites. According to the literature, <20 cases of primary gastric FL have been reported, with the number of cases with detailed pathological descriptions being even less. The aim of the present study was to compare clinicopathological features of gastric FL with FL at alternative sites. A total of 3 cases of gastric FL were retrieved from among 3,216 cases in the databases of 4 university hospitals in South Korea: Seoul National University (SNU) Hospital, SNU Boramae Hospital, SNU Bundang Hospital (all Seoul, South Korea) and Dongtan Sacred Heart Hospital Hallym University (Dongtan, South Korea), including 2 primary cases and 1 case that was possibly secondary to nodal FL...
July 2018: Oncology Letters
Simon Le Gallou, Zhicheng Zhou, Lan-Huong Thai, Remi Fritzen, Alba Verge de Los Aires, Jérôme Mégret, Philipp Yu, Daisuke Kitamura, Emmanuelle Bille, Fabiola Tros, Xavier Nassif, Alain Charbit, Sandra Weller, Jean-Claude Weill, Claude-Agnès Reynaud
To what extent immune responses against the gut flora are compartmentalized within mucosal tissues in homeostatic conditions remains a much-debated issue. We describe here, based on an inducible AID fate-mapping mouse model, that systemic memory B cell subsets, including mainly IgM+ B cells in spleen, together with IgA+ plasma cells in spleen and bone marrow, are generated in mice in the absence of deliberate immunization. While the IgA component appears dependent on the gut flora, IgM memory B cells are still generated in germ-free mice, albeit to a reduced extent...
June 29, 2018: Journal of Experimental Medicine
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