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tertiary germinal center

Gareth W Jones, David G Hill, Simon A Jones
Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules...
2016: Frontiers in Immunology
Rakesh Reddy, Ajay Gogia, Lalit Kumar, Atul Sharma, Sameer Bakhshi, Mehar C Sharma, Saumyaranjan Mallick, Ranjit Sahoo
CONTEXT AND AIM: Data on HIV associated hematologic malignancies is sparse from India. This study attempts to analyze the spectrum and features of this disease at a tertiary cancer center in India. SETTING AND METHODS: Retrospective study from case records of patients registered with a diagnosis of hematologic malignancy and HIV infection between January 2010 and June 2015. RESULTS: Thirteen cases of HIV associated hematologic malignancies were identified, six of them pediatric...
July 2016: Indian Journal of Medical and Paediatric Oncology
Katrijn Neyt, Corine H GeurtsvanKessel, Kim Deswarte, Hamida Hammad, Bart N Lambrecht
Inducible bronchus-associated lymphoid tissue (iBALT) is a long lasting tertiary lymphoid tissue that can be induced following influenza A virus (IAV) infection. Previous studies have shown that iBALT structures containing germinal center (GC) B cells protect against repeated infection by contributing locally to the cellular and humoral immune response. If we are to exploit this in vaccination strategies, we need a better understanding on how iBALT structures are induced. One hypothesis is that the strength of the initial innate response dictates induction of iBALT...
2016: Frontiers in Immunology
Jan Kranich, Nike Julia Krautler
Follicular dendritic cells (FDCs) are stromal cells residing in primary follicles and in germinal centers of secondary and tertiary lymphoid organs (SLOs and TLOs). There, they play a crucial role in B-cell activation and affinity maturation of antibodies. FDCs have the unique capacity to bind and retain native antigen in B-cell follicles for long periods of time. Therefore, FDCs shape the B-cell antigenome (the sum of all B-cell antigens) in SLOs and TLOs. In this review, we discuss recent findings that explain how this stromal cell type can arise in almost any tissue during TLO formation and, furthermore, focus on the mechanisms of antigen capture and retention involved in the generation of long-lasting antigen depots displayed on FDCs...
2016: Frontiers in Immunology
Marc Clement, Adrien Galy, Patrick Bruneval, Marion Morvan, Fabien Hyafil, Khadija Benali, Nicoletta Pasi, Lydia Deschamps, Quentin Pellenc, Thomas Papo, Antonino Nicoletti, Karim Sacre
OBJECTIVE: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. METHODS: Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry...
2016: Frontiers in Immunology
Giovanni Francesco Castino, Nina Cortese, Giovanni Capretti, Simone Serio, Giuseppe Di Caro, Rossana Mineri, Elena Magrini, Fabio Grizzi, Paola Cappello, Francesco Novelli, Paola Spaggiari, Massimo Roncalli, Cristina Ridolfi, Francesca Gavazzi, Alessandro Zerbi, Paola Allavena, Federica Marchesi
B-cell responses are emerging as critical regulators of cancer progression. In this study, we investigated the role of B lymphocytes in the microenvironment of human pancreatic ductal adenocarcinoma (PDAC), in a retrospective consecutive series of 104 PDAC patients and in PDAC preclinical models. Immunohistochemical analysis revealed that B cells occupy two histologically distinct compartments in human PDAC, either scatteringly infiltrating (CD20-TILs), or organized in tertiary lymphoid tissue (CD20-TLT). Only when retained within TLT, high density of B cells predicted longer survival (median survival 16...
April 2016: Oncoimmunology
Prasad Srikakulapu, Desheng Hu, Changjun Yin, Sarajo K Mohanta, Sai Vineela Bontha, Li Peng, Michael Beer, Christian Weber, Coleen A McNamara, Gianluca Grassia, Pasquale Maffia, Rudolf A Manz, Andreas J R Habenicht
OBJECTIVE: Explore aorta B-cell immunity in aged apolipoprotein E-deficient (ApoE(-/-)) mice. APPROACH AND RESULTS: Transcript maps, fluorescence-activated cell sorting, immunofluorescence analyses, cell transfers, and Ig-ELISPOT (enzyme-linked immunospot) assays showed multilayered atherosclerosis B-cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B-cell-related transcriptomes were identified, and transcript atlases revealed highly territorialized B-cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B-cell genes, including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm although intima plaques preferentially expressed molecules involved in non-B effector responses toward B-cell-derived mediators, that is, Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family...
June 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Marie-Caroline Dieu-Nosjean, Nicolas A Giraldo, Hélène Kaplon, Claire Germain, Wolf Herman Fridman, Catherine Sautès-Fridman
The characterization of the microenvironment of human tumors led to the description of tertiary lymphoid structures (TLS) characterized by mature dendritic cells in a T-cell zone adjacent to B-cell follicle including a germinal center. TLS represent sites of lymphoid neogenesis that develop in most solid cancers. Analysis of the current literature shows that the TLS presence is associated with a favorable clinical outcome for cancer patients, regardless of the approach used to quantify TLS and the stage of the disease...
May 2016: Immunological Reviews
Nicolas Delaleu, Piotr Mydel, Johan G Brun, Malin V Jonsson, Andrea Alimonti, Roland Jonsson
OBJECTIVE: Clinical expression of SS shows considerable interpatient heterogeneity. Thus, the aim of this study was to assess whether individual salivary proteomic profiles provide a framework for identification of disease-phenotype-driven biomarker signatures. METHODS: Using a 187-plex capture antibody-based assay, proteomic biomarker profiles from unstimulated whole saliva were generated from a SS-cohort representing six clinically distinct disease phenotypes...
June 2016: Rheumatology
Jennifer L Kielczewski, Reiko Horai, Yingyos Jittayasothorn, Chi-Chao Chan, Rachel R Caspi
During chronic inflammation, tertiary lymphoid tissue (TLT) can form within an inflamed organ, including the CNS. However, little is known about TLT formation in the neuroretina. In a novel spontaneous autoimmune mouse model of uveitis (R161H), we identified well-organized lymphoid aggregates in the retina and examined them for TLT characteristics. Presence of immune cells, tissue-specific markers, and gene expression patterns typically associated with germinal centers and T follicular helper cells were examined using immunohistochemistry and gene analysis of laser capture microdissected retina...
February 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Xiaoguang Xu, Yong Han, Qiang Wang, Ming Cai, Yeyong Qian, Xinying Wang, Haiyan Huang, Liang Xu, Li Xiao, Bingyi Shi
PURPOSE: Tertiary lymphoid organs (TLOs) have been described within organ allografts, but whether they promote destructive or beneficial alloimmune responses remains controversial. This study aimed to characterize TLO distribution in human chronically rejected renal allografts and to explore their functions. METHODS: A total of 29 explanted chronically rejected and 12 acutely rejected renal allografts were analyzed by immunohistochemistry. The distribution of TLOs, T cells, follicular dendritic cells, B cells, and follicular regulatory T (Tfr) cells, as well as Ki67, peripheral lymph node addressin (PNAd), podoplanin, AID, IL-17, IL-21, IL-10, and C4d expression were detected by immunohistochemistry...
2016: Immunological Investigations
G H Tse, C J C Johnston, D Kluth, M Gray, D Gray, J Hughes, L P Marson
Renal transplantation is the optimum treatment for end-stage renal failure. B cells have been identified in chronic allograft damage (CAD) and associated with the development of tertiary lymphoid tissue within the human renal allograft. We performed renal transplantation in mice to model CAD and identified B cells forming tertiary lymphoid tissue with germinal centers. Intra-allograft B220(+) B cells comprised of IgM(high) CD23(-) B cells, IgM(lo) CD23(+) B cells, and IgM(lo) CD23(-) B cells with elevated expression of CD86...
December 2015: American Journal of Transplantation
Bimal Patel, Geeta Chacko, Sheila Nair, Jamie Anandan, Ari G Chacko, Vedantam Rajshekhar, Mazda Turel
BACKGROUND: Primary central nervous system lymphomas (PCNSL) constitute a rare group of extranodal non-Hodgkin's lymphomas (NHLs). AIM: To study the clinical and immunophenotypic profile of patients with a PCNSL who presented between the years 2000 and 2013 in a tertiary care center in South India. MATERIALS AND METHODS: This was a retrospective study. Demographic and clinical data were obtained from the clinical case records. INCLUSION CRITERIA: Cases of PCNSL involving brain...
January 2015: Neurology India
Radha Thyagarajan, Viqar Banday, Zhoujie Ding, Kristina Lejon
The immunoglobulin isotype IgE is commonly associated with allergy. However, its involvement in autoimmune disease in general, and Type 1 diabetes (T1D) in particular, is still not completely clarified, nonetheless IgE has been observed in patients with T1D. In this article, we aimed to elucidate the contribution of IgE in the pathogenesis of the disease in a spontaneous model for T1D, i.e. the NOD mouse. We observed increased levels of IgE in splenic, lymph node and peripheral blood B cells in the NOD mice compared to the control C57BL/6 (B6) mice...
2015: Autoimmunity
Marc Clement, Kevin Guedj, Francesco Andreata, Marion Morvan, Laetitia Bey, Jamila Khallou-Laschet, Anh-Thu Gaston, Sandrine Delbosc, Jean-Marc Alsac, Patrick Bruneval, Catherine Deschildre, Marie Le Borgne, Yves Castier, Hye-Jung Kim, Harvey Cantor, Jean-Baptiste Michel, Giuseppina Caligiuri, Antonino Nicoletti
BACKGROUND: The atheromodulating activity of B cells during the development of atherosclerosis is well documented, but the mechanisms by which these cells are regulated have not been investigated. METHODS AND RESULTS: Here, we analyzed the contribution of Qa-1-restricted CD8(+) regulatory T cells to the control of the T follicular helper-germinal center B-cell axis during atherogenesis. Genetic disruption of CD8(+) regulatory T cell function in atherosclerosis-prone apolipoprotein E knockout mice resulted in overactivation of this axis in secondary lymphoid organs, led to the increased development of tertiary lymphoid organs in the aorta, and enhanced disease development...
February 10, 2015: Circulation
Marie-Caroline Dieu-Nosjean, Jérémy Goc, Nicolas A Giraldo, Catherine Sautès-Fridman, Wolf Herman Fridman
Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts...
November 2014: Trends in Immunology
Coco Chu, Yifeng Wang, Xu Zhang, Xinya Ni, Junxia Cao, Wan Xu, Zhongjun Dong, Pengfei Yuan, Wensheng Wei, Yuanwu Ma, Lianfeng Zhang, Longyan Wu, Hai Qi
The germinal center response requires cooperation between Ag-specific T and B lymphocytes, which takes the form of long-lasting cell-cell conjugation in vivo. Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is required for stable cognate T-B cell conjugation, whereas SLAM family transmembrane (TM) receptor Ly108 may negatively regulate this process. We show that, other than phosphotyrosine-binding, SAP does not harbor motifs that recruit additional signaling intermediates to stabilize T-B adhesion...
October 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Chuanxin Huang, David G Gonzalez, Christine M Cote, Yanwen Jiang, Katerina Hatzi, Matt Teater, Kezhi Dai, Timothy Hla, Ann M Haberman, Ari Melnick
To understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2(MUT) mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2(MUT) antigen-engaged B cells migrate to the interfollicular zone and interact with cognate T helper cells. However, these cells fail to complete early GC-commitment differentiation and coalesce as nascent GC aggregates. Bcl6 directly binds and represses trafficking receptors S1pr1 and Gpr183 by recruiting Hdac2 through the RD2 domain...
September 11, 2014: Cell Reports
Jodi L Karnell, Tamer I Mahmoud, Ronald Herbst, Rachel Ettinger
Ectopic follicles are non-encapsulated organized lymphoid structures that form at sites of inflammation and presumably contribute to the activation and differentiation of cells with autoreactive potential within target tissues. As such, directed targeting of ectopic follicles in settings of autoimmunity may provide a means to specifically inhibit the activation of autoreactive cells without impairing protective immune responses ongoing in peripheral lymphoid tissues. NOD·H2h4 mice are a non-diabetic strain of NOD mice which develop a Sjögren's syndrome-like disease which includes the formation of ectopic follicles in the salivary gland and characteristic Sjögren's autoantibodies...
December 2014: Molecular Immunology
Sarajo Kumar Mohanta, Changjun Yin, Li Peng, Prasad Srikakulapu, Vineela Bontha, Desheng Hu, Falk Weih, Christian Weber, Norbert Gerdes, Andreas J R Habenicht
Tertiary lymphoid organs emerge in tissues in response to nonresolving inflammation. Recent research characterized artery tertiary lymphoid organs in the aorta adventitia of aged apolipoprotein E-deficient mice. The atherosclerosis-associated lymphocyte aggregates are organized into distinct compartments, including separate T-cell areas harboring conventional, monocyte-derived, lymphoid, and plasmacytoid dendritic cells, as well as activated T-cell effectors and memory cells; B-cell follicles containing follicular dendritic cells in activated germinal centers; and peripheral niches of plasma cells...
May 23, 2014: Circulation Research
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