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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/28801669/balance-between-estrogens-and-proinflammatory-cytokines-regulates-chemokine-production-involved-in-thymic-germinal-center-formation
#5
Nadine Dragin, Patrice Nancy, José Villegas, Régine Roussin, Rozen Le Panse, Sonia Berrih-Aknin
The early-onset form of Myasthenia Gravis (MG) is prevalent in women and associates with ectopic germinal centers (GCs) development and inflammation in the thymus. we aimed to investigate the contribution of estrogens in the molecular processes involved in thymic GCs formation. We examined expression of genes involved in anti-acetylcholine receptor (AChR) response in MG, MHC class II and α-AChR subunit as well as chemokines involved in GC development (CXCL13, CCL21and CXCL12). In resting conditions, estrogens have strong regulatory effects on thymic epithelial cells (TECs), inducing a decreased protein expression of the above molecules...
August 11, 2017: Scientific Reports
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
#6
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/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/28779693/extrafollicular-activities-perspectives-on-hiv-infection-germinal-center-independent-maturation-pathways-and-kshv-mediated-lymphoproliferation
#9
REVIEW
Jennifer Totonchy
Early events in the pathogenesis of KSHV-associated lymphoproliferations in the context of HIV disease remain poorly understood. Recent research indicates that latent HIV infection causes persistent immune dysfunction in B cell follicles. Simultaneously, lack of T cell immune surveillance in the lymph nodes dysregulates the biology of EBV. In sum, these defects bias B lymphocyte maturation away from traditional T cell-dependent germinal center-mediated pathways and towards extrafollicular pathways. Recent advances in B lymphocyte immunology suggest that extrafollicular maturation pathways for antibody secreting cells are more flexible and robust than previously believed...
August 2, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28769932/melanomacrophage-centers-as-a-histological-indicator-of-immune-function-in-fish-and-other-poikilotherms
#10
REVIEW
Natalie C Steinel, Daniel I Bolnick
Melanomacrophage centers (MMCs) are aggregates of highly pigmented phagocytes found primarily in the head kidney and spleen, and occasionally the liver of many vertebrates. Preliminary histological analyses suggested that MMCs are structurally similar to the mammalian germinal center (GC), leading to the hypothesis that the MMC plays a role in the humoral adaptive immune response. For this reason, MMCs are frequently described in the literature as "primitive GCs" or the "evolutionary precursors" to the mammalian GC...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28769068/synergistic-strategy-for-multicolor-two-photon-microscopy-application-to-the-analysis-of-germinal-center-reactions-in-vivo
#11
Asylkhan Rakhymzhan, Ruth Leben, Hanna Zimmermann, Robert Günther, Peggy Mex, David Reismann, Carolin Ulbricht, Andreas Acs, Alexander U Brandt, Randall L Lindquist, Thomas H Winkler, Anja E Hauser, Raluca A Niesner
Simultaneous detection of multiple cellular and molecular players in their native environment, one of the keys to a full understanding of immune processes, remains challenging for in vivo microscopy. Here, we present a synergistic strategy for spectrally multiplexed in vivo imaging composed of (i) triple two-photon excitation using spatiotemporal synchronization of two femtosecond lasers, (ii) a broad set of fluorophores with emission ranging from blue to near infrared, (iii) an effective spectral unmixing algorithm...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768709/co-stimulatory-function-in-primary-germinal-center-responses-cd40-and-b7-are-required-on-distinct-antigen-presenting-cells
#12
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/28768471/unsuspected-human-immunodeficiency-virus-infection-presenting-as-immunoglobulin-g4-related-lymphadenopathy-a-case-report
#13
Hsing-Tse Yu, Chen-Hsiang Lee, Shun-Chen Huang, Shan-Fu Yu
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition characterized by infiltration of the involved organs by IgG4-bearing plasma cells. The prevalence of autoimmune diseases, associated with or occurring in patients with human immunodeficiency virus (HIV) infection, has been increasing. We describe a 58-year-old man with an undiagnosed HIV infection, which presented as chronic cervical lymphadenopathy with an elevated serum IgG4 and a very high IgE. Histologically, lymph nodes showed expanded sinusoids and burnt-out germinal centers with increased plasmacytic infiltration and collagen fiber deposition...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28767707/murine-gammaherpesvirus-m2-antigen-modulates-splenic-b-cell-activation-and-terminal-differentiation-in-vivo
#14
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
#15
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/28760610/macrophage-derived-insulin-like-growth-factor-1-affects-influenza-vaccine-efficacy-through-the-regulation-of-immune-cell-homeostasis
#16
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
#17
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
#18
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/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/28748511/unique-histologic-features-of-tonsils-from-patients-with-periodic-fever-aphthous-stomatitis-pharyngitis-and-cervical-adenitis-pfapa-syndrome
#20
Kalpana Manthiram, Hernan Correa, Kelli Boyd, Joseph Roland, Kathryn Edwards
The objective of this study is to compare the histology and immune cell composition of tonsils from patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome to those from patients with obstructive sleep apnea (OSA). Patients with PFAPA and age-matched controls with OSA who had undergone tonsillectomy at Vanderbilt Children's Hospital were recruited. After informed consent, archival paraffin-embedded, formalin-fixed tonsil tissues were obtained. Sizes of major histologic regions were measured...
July 26, 2017: Clinical Rheumatology
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