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Germinal center reaction

Dillon C Schrock, Scott A Leddon, Angela Hughson, Jim Miller, Adam Lacy-Hulbert, Deborah J Fowell
CD4+ follicular helper T cells (Tfh) are essential for germinal center (GC) reactions in the lymph node that generate high-affinity, long-lived plasma cells (LLPCs). Temporal GC analysis suggests B memory cells (Bmem) are generated early, while LLPCs are generated late in the GC reaction. Distinct roles for Tfh at these temporally different stages are not yet clear. Tfh entry into the GC is highly dynamic and the signals that maintain Tfh within the GC for support of late LLPC production are poorly understood...
February 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
Julia Bier, Geetha Rao, Kathryn Payne, Henry Brigden, Elise French, Simon J Pelham, Anthony Lau, Helen Lenthall, Emily S J Edwards, Joanne M Smart, Theresa S Cole, Sharon Choo, Avni Y Joshi, Roshini S Abraham, Michael O'Sullivan, Kaan Boztug, Isabelle Meyts, Paul E Gray, Lucinda J Berglund, Peter Hsu, Melanie Wong, Steven M Holland, Luigi D Notarangelo, Gulbu Uzel, Cindy S Ma, Robert Brink, Stuart G Tangye, Elissa K Deenick
BACKGROUND: Gain of function (GOF) mutations in PIK3CD cause a primary immunodeficiency characterized by recurrent respiratory tract infections, susceptibility to herpes virus infections and impaired antibody responses. Previous work revealed defects in CD8+ T and B cells that contribute to this clinical phenotype but less is understood about the role of CD4+ T cells in disease pathogenesis. OBJECTIVE: To dissect the effects of increased phosphoinositide-3 kinase (PI3K) signaling on CD4+ T cell function...
February 6, 2019: Journal of Allergy and Clinical Immunology
Rintaro Ohe, Hong-Xue Meng, Naing Ye Aung, Akane Yamada, Takanobu Kabasawa, Aya Utsunomiya, Nobuyuki Tamazawa, Yuka Tamura, Takumi Kitaoka, Toshio Hashimoto, Kenichi Shibata, Tomomi Toubai, Wataru Kimura, Kenichi Ishizawa, Mitsunori Yamakawa
Hormone therapy has been used for patients with estrogen receptor alpha (ERα)-positive breast cancers. Recently, some studies reported the expression of ERα on neoplastic cells from B cell lymphomas. However, there has been only one report of ERα expression on the follicular dendritic cells (FDCs) that structurally and functionally support the microenvironment of follicular lymphomas (FLs). The objective of this study was to investigate the frequency of ERα expression on FDCs in nonneoplastic reactive lymphoid tissues and to compare the frequency of ERα expression on FDCs in the axillary lymph nodes between patients with and without antiestrogen therapy and among patients with grades 1-3 of FL...
February 8, 2019: Hematological Oncology
Joseph N Pucella, Montserrat Cols, Wei-Feng Yen, Shunbin Xu, Jayanta Chaudhuri
Although primary humoral responses are vital to durable immunity, fine-tuning is critical to preventing catastrophes such as autoimmunity, chronic inflammation, and lymphomagenesis. MicroRNA (miRNA)-mediated regulation is particularly well suited for fine-tuning roles in physiology. Expression of clustered paralogous miR-182, miR-96, and miR-183 (collectively, 183c) is robustly induced upon B cell activation, entry into the germinal center, and plasmablast differentiation. 183cGT/GT mice lacking 183c miRNA expression exhibit largely normal primary humoral responses, encompassing class switch recombination, affinity maturation, and germinal center reaction, as well as plasmablast differentiation...
January 25, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Michele Proietti, Lisa Perruzza, Daniela Scribano, Giovanni Pellegrini, Rocco D'Antuono, Francesco Strati, Marco Raffaelli, Santiago F Gonzalez, Marcus Thelen, Wolf-Dietrich Hardt, Emma Slack, Mauro Nicoletti, Fabio Grassi
T cell dependent secretory IgA (SIgA) generated in the Peyer's patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host's immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells expansion and germinal center (GC) reaction in the PPs. Here we show that transient depletion of intestinal ATP can dramatically improve high-affinity IgA response against both live and inactivated oral vaccines...
January 16, 2019: Nature Communications
Michael A Richardson, Tuddow Thaiwong, Matti Kiupel
Primary colorectal follicular lymphomas are rare indolent lymphoid neoplasms in humans that have not been reported in dogs. We describe 3 cases of primary colorectal follicular lymphoma in dogs with histologic and immunohistochemical features similar to their human counterpart. Initial clinical signs in all dogs included tenesmus, hematochezia, and a palpable rectal mass. Two dogs were castrated males and 1 an intact female, between 9 months and 2 years of age, and of varied breeds. All 3 cases of colorectal follicular lymphoma were characterized by proliferation of follicular germinal centers with no polarity or mantle zone and were composed of centrocytes admixed with fewer centroblasts...
January 13, 2019: Veterinary Pathology
Preethi Eldi, Geeta Chaudhri, Stephen L Nutt, Timothy P Newsome, Gunasegaran Karupiah
Live viral vaccines elicit protective, long-lived humoral immunity but the underlying mechanisms through which this occurs are not fully elucidated. Generation of affinity matured, long-lived protective antibody responses involve close interactions between T follicular helper (TFH ) cells, germinal center (GC) B cells, and T follicular regulatory (TFR ) cells. We postulated that escalating concentrations of antigens from replicating viruses or live vaccines, spread through the hematogenous route, is essential for the induction and maintenance of long-lived protective antibody responses...
January 9, 2019: Journal of Virology
Marios Koutsakos, Thi H O Nguyen, Katherine Kedzierska
Influenza remains a global and unpredictable threat. Annual vaccination against influenza A and B viruses promotes the induction of Abs and memory B cells, which can provide strain-specific protection against subsequent infections. The formation of effective memory B cell and Ab responses is highly dependent on the germinal center reaction, a well-orchestrated process involving B cells and a specialized CD4+ T cell subset called T follicular helper (Tfh) cells. As Tfh cells predominantly reside within B cell follicles in secondary lymphoid organs, they are challenging to study in humans...
January 15, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Li Yuan, Wen-Jiang Chen, Jia-Ye Wang, Yan Li, Dan Tian, Ming-Xia Wang, Hao-Tong Yu, Ying-Chu Xu, Di Li, Min Zhuang, Hong Ling
The development of a vaccine based on human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) that elicits potent protective antibodies against infection has been challenging. Recently, we compared the antibody production patterns of HIV-1 Env gp120 and hepatitis B virus surface antigen (HBsAg) to provide insights into how we may improve the protective efficacy of Env-based immunogens. Our previous study showed that HIV Env and HBsAg display different mechanisms of antibody elicitation and that T cells facilitate the responses to repeated immunizations...
December 19, 2018: Virologica Sinica
M Saeed Qureshi, Jawaher Alsughayyir, Manu Chhabra, Jason M Ali, Martin J Goddard, Chris Devine, Thomas M Conlon, Michelle A Linterman, Reza Motallebzadeh, Gavin J Pettigrew
The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection. In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclear autoantibody responses were initiated upon graft-versus-host allorecognition of recipient B cells by donor CD4 T-cells transferred within heart allografts. Consequently, grafts were rejected more rapidly, and with markedly augmented autoantibody responses, upon transplantation of hearts from donors previously primed against recipient...
December 6, 2018: Journal of Autoimmunity
Anne Slomp, Victor Peperzak
Apoptosis plays a key role in protection against genomic instability and maintaining tissue homeostasis, and also shapes humoral immune responses. During generation of an antibody response, multiple rounds of B-cell expansion and selection take place in germinal centers (GC) before high antigen affinity memory B-cells and long-lived plasma cells (PC) are produced. These processes are tightly regulated by the intrinsic apoptosis pathway, and malignant transformation throughout and following the GC reaction is often characterized by apoptosis resistance...
2018: Frontiers in Oncology
Chiara Farroni, Emiliano Marasco, Valentina Marcellini, Ezio Giorda, Diletta Valentini, Stefania Petrini, Valentina D'Oria, Marco Pezzullo, Simona Cascioli, Marco Scarsella, Alberto G Ugazio, Giovanni C De Vincentiis, Ola Grimsholm, Rita Carsetti
Children with Down Syndrome (DS) suffer from immune deficiency with a severe reduction in switched memory B cells (MBCs) and poor response to vaccination. Chromosome 21 (HSA21) encodes two microRNAs (miRs), miR-125b, and miR-155, that regulate B-cell responses. We studied B- and T- cell subpopulations in tonsils of DS and age-matched healthy donors (HD) and found that the germinal center (GC) reaction was impaired in DS. GC size, numbers of GC B cells and Follicular Helper T cells (TFH ) expressing BCL6 cells were severely reduced...
2018: Frontiers in Immunology
Carter K Haag, Elizabeth Dacey, Nick Hamilton, Kevin P White
Reports detailing the acute formation of aluminum granulomas, which can cause persistent, intensely pruritic nodules secondary to the administration of aluminum-containing vaccines, are infrequently described in medical literature. To our knowledge, this is the first report describing the development of an aluminum granuloma causing a persistent, pruritic nodule at the injection site following the administration of the DTaP-IPV vaccine. We present the case of a 6-year-old girl who developed a severely pruritic subcutaneous nodule on her anterior right thigh at the injection site three weeks after the administration of the aluminum-containing DTaP-IPV (Kinrix) vaccine...
November 28, 2018: Pediatric Dermatology
O V Kazakov, A V Kabakov, A F Poveshchenko, T V Raiter, D N Strunkin, O V Poveshchenko, A P Lykov, V I Konenkov
The morphometric analysis of mesenteric lymph nodes was carried out in female Wistar rats with chemically induced breast cancer. In control rats with untreated breast cancer, the volume of the system of sinuses increased in parallel with the appearance of morphological signs of suppression of cell-mediated immunity, inhibition of humoral immunity, and macrophage reaction. Against the background of chemotherapy, we observed a decrease in the volume of paracortex and lymphoid nodules, suppression of proliferative activity of lymphoid cells in paracortical and B-cell zone, and a decrease in macrophage content...
December 2018: Bulletin of Experimental Biology and Medicine
Gang Xin, Ryan Zander, David M Schauder, Yao Chen, Jason S Weinstein, William R Drobyski, Vera Tarakanova, Joseph Craft, Weiguo Cui
During chronic viral infection, the inflammatory function of CD4 T-cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T-cells during chronic infection. Here we show an IL-10-producing population with a robust Tfh-signature...
November 28, 2018: Nature Communications
Marcela Parra, Jiyeon Yang, Megan Weitner, Steven Derrick, Amy Yang, Thomas Schmidt, Balwan Singh, Alberto Moreno, Mustafa Akkoyunlu
The delay in parasite-specific B cell development leaves people in malaria endemic areas vulnerable to repeated Plasmodium infections. Here, we investigated the role of transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), a molecule involved in the generation of antigen-specific antibody secreting cells, in host response to non-lethal Plasmodium yoelii infection. We found that TACI deficiency not only resulted in higher peak parasitemia levels in P. yoelii challenged mice, but also led to a delay in parasite clearance and anti- P...
2018: Frontiers in Immunology
Sabrina Helmold Hait, Diego A Vargas-Inchaustegui, Thomas Musich, Venkatramanan Mohanram, Iskra Tuero, David J Venzon, Jenifer Bear, Margherita Rosati, Monica Vaccari, Genoveffa Franchini, Barbara K Felber, George N Pavlakis, Marjorie Robert-Guroff
T follicular helper (TFH ) cells are fundamental in germinal center (GC) maturation and selection of antigen-specific B cells within secondary lymphoid organs. GC-resident TFH cells have been fully characterized in human HIV infection. However, the role of GC TFH cells in GC B cell responses following various SIV vaccine regimens in Rhesus macaques (RMs) has not been fully investigated. We characterized GC TFH cells of RMs over the course of a mucosal/systemic vaccination regimen to elucidate GC formation and SIV humoral response generation...
November 21, 2018: Journal of Virology
Marisa Stebegg, Saumya D Kumar, Alyssa Silva-Cayetano, Valter R Fonseca, Michelle A Linterman, Luis Graca
The germinal center (GC) is a specialized microstructure that forms in secondary lymphoid tissues, producing long-lived antibody secreting plasma cells and memory B cells, which can provide protection against reinfection. Within the GC, B cells undergo somatic mutation of the genes encoding their B cell receptors which, following successful selection, can lead to the emergence of B cell clones that bind antigen with high affinity. However, this mutation process can also be dangerous, as it can create autoreactive clones that can cause autoimmunity...
2018: Frontiers in Immunology
Timm Weber, Jane Seagal, Wiebke Winkler, Tristan Wirtz, Van Trung Chu, Klaus Rajewsky
The germinal center reaction is essential for efficient humoral immunity, but it can also give rise to B cell lymphomas. Cre/loxP-mediated conditional gene knock-out or knock-in can be used for the genetic manipulation of germinal center B cells in vivo. Here we present a novel allele, Cγ1-CreERT2, that allows for timed activation of Cre recombinase in a small fraction of germinal center B cells. This allele will be useful to study normal and malignant germinal center B cell development in vivo. This article is protected by copyright...
October 25, 2018: European Journal of Immunology
Jeffrey R Atkinson, Mihyun Hwang, Angel Reyes-Rodriguez, Cornelia C Bergmann
Humoral responses within the central nervous system (CNS) are common to many neurotropic viral infections, with antibody (Ab) secreting cells (ASC) contributing to local protection. However, a role for virus-specific memory B cells (Bmem) within the CNS is poorly explored due to lack of robust phenotypic or functional identification in mice. This study takes advantage of mice expressing tamoxifen-inducible Cre recombinase (Cre-ERT2) under the Aicda promoter crossed with Rosa26-loxP-tdTomato reporter mice (AIDCre -Rosa26tdTomato ) to monitor B cells having undergone activation-induced cytidine deaminase (AID)-mediated somatic hypermutation (SHM) following neurotropic coronavirus infection...
October 17, 2018: Journal of Virology
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