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Germinal center reaction

Lan He, Wangpeng Gu, Meng Wang, Xiaoyan Chang, Xiaoyu Sun, Yuan Zhang, Xuan Lin, Chenghua Yan, Weiguo Fan, Pan Su, Yanming Wang, Chunyan Yi, Guomei Lin, Li Li, Yu Jiang, Junxia Lu, Chen Dong, Haikun Wang, Bing Sun
T-follicular helper (TFH ) cells are a subset of CD4+ helper T cells that help germinal center (GC) B-cell differentiation and high-affinity antibody production during germinal center reactions. Whether important extracellular molecules control TFH differentiation is not fully understood. Here, we demonstrate that a secreted protein extracellular matrix protein 1 (ECM1) is critical for TFH differentiation and antibody response. A lack of ECM1 inhibited TFH cell development and impaired GC B-cell reactions and antigen-specific antibody production in an antigen-immunized mouse model...
August 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Andreas Hutloff
T and B cell cooperation normally takes place in secondary lymphoid organs (SLO). However, both cell types are also frequently found in inflamed non-lymphoid tissues. Under certain conditions, these infiltrates develop into ectopic lymphoid structures, also known as tertiary lymphoid tissues, which structurally and functionally fully resemble germinal centers (GCs) in SLO. However, tertiary lymphoid tissue is uncommon in most human autoimmune conditions; instead, relatively unstructured T and B cell infiltrates are found...
2018: Frontiers in Immunology
Xiaoqing Lu, Tharu Fernando, Chen Lossos, Nevin Yusufova, Fan Liu, Lorena Fontán, Matthew Durant, Huimin Geng, Jacob Melnick, Yuan Luo, Francisco Vega, Vincent Moy, Giorgio Inghirami, Stephen Nimer, Ari M Melnick, Izidore S Lossos
The Germinal Center (GC) reaction plays an important role in generating humoral immunity and is believed to give rise to most B-cell lymphomas. GC entry and exit are tightly regulated processes, controlled by the actions of transcription factors such as BCL6. Herein we demonstrate that PRMT5, a symmetric dimethyl arginine methyltransferase, is also necessary for GC formation and affinity maturation. PRMT5 contributes to GC formation and affinity maturation at least in part through its direct interaction with and methylation of BCL6 at arginine 305 (R305), a modification necessary for the full transcriptional repressive effects of BCL6...
August 6, 2018: Blood
Noémie Gensous, Manon Charrier, Dorothée Duluc, Cécile Contin-Bordes, Marie-Elise Truchetet, Estibaliz Lazaro, Pierre Duffau, Patrick Blanco, Christophe Richez
T follicular helper (Tfh) cells are a distinct subset of CD4+ T lymphocytes, specialized in B cell help and in regulation of antibody responses. They are required for the generation of germinal center reactions, where selection of high affinity antibody producing B cells and development of memory B cells occur. Owing to the fundamental role of Tfh cells in adaptive immunity, the stringent control of their production and function is critically important, both for the induction of an optimal humoral response against thymus-dependent antigens but also for the prevention of self-reactivity...
2018: Frontiers in Immunology
Alberto Purwada, Shivem B Shah, Wendy Béguelin, Avery August, Ari M Melnick, Ankur Singh
Most antigen discovery and vaccine development aimed at driving functional B cell responses rely on mouse immunizations studies. To date, there is no 3D ex vivo immune tissues, which are capable of driving antigen-specific B cell responses to rapidly determine the humoral immunogenicity of antigens, understand the role of extracellular matrix in humoral immunity, and generate high affinity antibody responses. This can be attributed to the complexity of B cell differentiation and affinity maturation process in the germinal center (GC) reaction, which makes these highly specialized cells susceptible to rapid apoptosis ex vivo...
June 26, 2018: Biomaterials
Heeju Ryu, Yeonseok Chung
Cardiovascular disease such as atherosclerosis is caused by imbalanced lipid metabolism and represents a leading cause of death worldwide. Epidemiological studies show that patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate the incidence of autoimmune diseases in humans and in animal models. However, there is a considerable gap in our understanding of how atherosclerosis impacts the development of the autoimmunity in humans, and vice versa...
July 24, 2018: BMB Reports
Thomas Weisenburger, Bettina von Neubeck, Andrea Schneider, Nadja Ebert, Daniel Schreyer, Andreas Acs, Thomas H Winkler
Autoantibodies against double-stranded DNA (anti-dsDNA) are a hallmark of systemic lupus erythematosus (SLE). It is well documented that anti-dsDNA reactive B lymphocytes are normally controlled by immune self-tolerance mechanisms operating at several levels. The evolution of high levels of IgG anti-dsDNA in SLE is dependent on somatic hypermutation and clonal selection, presumably in germinal centers from non-autoreactive B cells. Twin studies as well as genetic studies in mice indicate a very strong genetic contribution for the development of anti-dsDNA as well as SLE...
2018: Frontiers in Immunology
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
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
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
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
Vijayakumar Velu, Geetha Mylvaganam, Chris Ibegbu, Rama Rao Amara
T follicular helper CD4 cells (Tfh) are essential for the development and maintenance of germinal center (GC) reactions, a critical process that promotes the generation of long-lived high affinity humoral immunity. It is becoming increasingly evident that GC-Tfh cells are heterogeneous in nature with some cellular characteristics associated with a Th1, Th2, and Th17 phenotype. Emerging studies suggest that GC-Tfh cells are directed to differentiate into distinct phenotypes during chronic HIV/SIV infection and these changes in GC-Tfh cells can greatly impact the B cell response and subclass of antibodies generated...
2018: Frontiers in Immunology
Elizabeth F Wallin, Danika L Hill, Michelle A Linterman, Kathryn J Wood
Background: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. Methods: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation...
2018: Frontiers in Immunology
Jeong Mi Yang, Ji-Young Jang, Yoon Kyung Jeon, Jin Ho Paik
BACKGROUND: Diffuse large B cell lymphoma (DLBCL) contains heterogeneous subtypes with various molecular dysregulation at the gene, protein and microRNA levels. Compared with the GCB subtype, the non-germinal center B-like (non-GCB)/activated B cell-like (ABC) subtype exhibits frequent progression despite standard immunochemotherapy. We aimed to investigate the effects of miR-197 on the progression and chemosensitivity of DLBCL with respect to the GCB and non-GCB/ABC subtypes. METHODS: To screen distinctively expressed microRNAs, microRNA expression patterns were analyzed in 10 DLBCL cases by microarray chip assays...
June 11, 2018: Journal of Translational Medicine
Ute Greczmiel, Annette Oxenius
Chronic infections with non-cytopathic viruses constitutively expose virus-specific adaptive immune cells to cognate antigen, requiring their numeric and functional adaptation. Virus-specific CD8 T cells are compromised by various means in their effector functions, collectively termed T cell exhaustion. Alike CD8 T cells, virus-specific CD4 Th1 cell responses are gradually downregulated but instead, follicular T helper (TFH ) cell differentiation and maintenance is strongly promoted during chronic infection...
2018: Frontiers in Immunology
Marco Puthenparampil, Antonio Zito, Giorgia Pantano, Lisa Federle, Erica Stropparo, Silvia Miante, Giustina De Silvestro, Mario Plebani, Paolo Gallo
BACKGROUND: Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell. OBJECTIVE: To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis...
June 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Kwame Doh, Ibou Thiam, Romulus Carmen Adechina Takin, Khaled Sonhaye, Gisèle Woto-Gaye
INTRODUCTION: Sebaceous lymphadenoma of the parotid (SLP) is a rare, benign tumor with similar epidemiological and macroscopic characteristics with other sebaceous differentiated tumors of the parotid (SDTP). The authors report a case of SLP in an 80-year-old woman. They then recall the distinctive histological and immunohistochemical criteria of SDTP. OBSERVATION: Mrs P. D. was received during a surgical consultation for the management of a painless right parotid swelling that has evolved for 10years, increasing slightly in volume...
June 4, 2018: Annales de Pathologie
Yaxing Hao, Yifei Wang, Xiaobing Liu, Xia Yang, Pengcheng Wang, Qin Tian, Qiang Bai, Xiangyu Chen, Zhirong Li, Jialin Wu, Zhunyi Xie, Xinyuan Zhou, Yuyang Zhou, Zhinan Yin, Yuzhang Wu, Lilin Ye
Follicular helper CD4+ T (TFH ) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of TFH cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate TFH differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific TFH cells...
2018: Frontiers in Immunology
Zhanshan Cha, Haihui Gu, Yan Zang, Zi Wang, Jinqi Li, Weihua Huang, Aihua Qin, Lishuang Zhu, Xiaohua Tu, Ning Cheng, Haihan Song, Baohua Qian
CD4+ CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells possess critical roles in suppressing the germinal center reaction, B cell activation, and follicular helper T cell (Tfh) cytokine secretion. Since diffuse large B cell lymphoma (DLBCL) can arise from B cells undergoing germinal center reaction and/or differentiation, we hypothesized that Tfr cells might be involved in DLBCL. In the present study, we recruited thirty-five DLBCL patients and twenty-five healthy controls. Data showed that DLBCL patients presented an enrichment of circulating CD4+ CXCR5+ Foxp3+ Tfr cells compared to controls...
August 2018: International Immunopharmacology
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