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Germinal center reaction

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
Michael Meyer-Hermann, Sebastian C Binder, Luka Mesin, Gabriel D Victora
Clonal evolution of B cells in germinal centers (GCs) is central to affinity maturation of antibodies in response to pathogens. Permanent or tamoxifen-induced multi-color recombination of B cells based on the brainbow allele allows monitoring the degree of color dominance in the course of the GC reaction. Here, we use computer simulations of GC reactions in order to replicate the evolution of color dominance in silico and to define rules for the interpretation of these data in terms of clonal dominance. We find that a large diversity of clonal dominance is generated in simulated GCs in agreement with experimental results...
2018: Frontiers in Immunology
Haotian Mao, Mengying Chen, Yanqiu Su, Nan Wu, Ming Yuan, Shu Yuan, Marian Brestic, Marek Zivcak, Huaiyu Zhang, Yanger Chen
To investigate the evolutionary differences of wheat with different ploidy levels and octoploid Triticale, photosynthetic capacity, and antioxidant defenses system were compared within and between diploid, tetraploid and hexaploid wheat, and octoploid Triticale seedlings. The results showed that seed germination rate, chlorophyll content, and photochemical activity of photosystems, and the activities of antioxidative enzymes in hexaploid wheat and octoploid Triticale were significantly higher than in diploid and tetraploid wheat...
October 2, 2018: International Journal of Molecular Sciences
Katelyn Paz, Ryan Flynn, Jing Du, Jun Qi, Leo Luznik, Ivan Maillard, Kelli P MacDonald, Geoffrey R Hill, Jonathan S Serody, William J Murphy, Peter T Sage, Arlene H Sharpe, David Miklos, Corey S Culter, John Koreth, Joseph H Antin, Robert J Soiffer, Jerome Ritz, James E Bradner, Ari M Melnick, Bruce Blazar
Patient outcomes for steroid-dependent or -refractory cGVHD are poor and only ibrutinib has been FDA approved for this indication. cGVHD is often driven by the germinal center (GC) reaction, in which T follicular helper cells interact with GC B-cells to produce antibodies that are associated with disease pathogenesis. The transcriptional co-repressor BCL6 is a member of the BTB/POZ transcription factor family and master regulator of the immune cells in the GC reaction. We demonstrate that BCL6 expression in both donor T-cells and B-cells is necessary for cGVHD development, pointing to BCL6 as a therapeutic cGVHD target...
October 2, 2018: Blood
Carlos G Briseño, Ansuman T Satpathy, Jesse T Davidson, Stephen T Ferris, Vivek Durai, Prachi Bagadia, Kevin W O'Connor, Derek J Theisen, Theresa L Murphy, Kenneth M Murphy
CD4+ T follicular helper (TFH ) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for Notch2 -dependent cDC2s, but not Batf3 -dependent cDC1s or Klf4 -dependent cDC2s, in promoting TFH and GC B cell formation in response to sheep red blood cells and inactivated Listeria monocytogenes This effect was mediated independent of Il2ra and several Notch2 -dependent genes expressed in cDC2s, including Stat4 and Havcr2 Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation of MHC class II-restricted antigens, limiting the strength of CD4 T cell activation...
October 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Pilar M Dominguez, Hussein Ghamlouch, Wojciech Rosikiewicz, Parveen Kumar, Wendy Béguelin, Lorena Fontán, Martín A Rivas, Patrycja Pawlikowska, Marine Armand, Enguerran Mouly, Miguel Torres-Martin, Ashley S Doane, María T Calvo Fernandez, Matt Durant, Veronique Della-Valle, Matt Teater, Luisa Cimmino, Nathalie Droin, Saber Tadros, Samaneh Motanagh, Alan H Shih, Mark A Rubin, Wayne Tam, Iannis Aifantis, Ross L Levine, Olivier Elemento, Giorgio Inghirami, Michael R Green, Maria E Figueroa, Olivier A Bernard, Said Aoufouchi, Sheng Li, Rita Shaknovich, Ari M Melnick
: TET2 somatic mutations occur in ∼10% of diffuse large B-cell lymphomas (DLBCL) but are of unknown significance. Herein, we show that TET2 is required for the humoral immune response and is a DLBCL tumor suppressor. TET2 loss of function disrupts transit of B cells through germinal centers (GC), causing GC hyperplasia, impaired class switch recombination, blockade of plasma cell differentiation, and a preneoplastic phenotype. TET2 loss was linked to focal loss of enhancer hydroxymethylation and transcriptional repression of genes that mediate GC exit, such as PRDM1...
December 2018: Cancer Discovery
Kati Kiil, Julia Bein, Bianca Schuhmacher, Lorenz Thurner, Markus Schneider, Martin-Leo Hansmann, Sylvia Hartmann
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma that frequently shows a nodal growth pattern with abundant reactive B cells in the microenvironment. Early NLPHL cases can be particularly difficult to differentiate from progressively transformed germinal centers (PTGC). Since PTGC have been described to be IgG4 associated in a relatively high proportion of cases, the aim of the present study was to determine if IgG4 immunostaining can be helpful in the differential diagnosis between NLPHL and PTGC...
December 2018: Virchows Archiv: An International Journal of Pathology
Carolyn E Rydyznski, Stacey A Cranert, Julian Q Zhou, Heping Xu, Steven H Kleinstein, Harinder Singh, Stephen N Waggoner
Somatic hypermutation of immunoglobulin sequences in germinal center (GC) reactions must be optimized to elicit high-affinity, protective antibodies after vaccination. We expose natural killer (NK) cells as robust negative regulators of somatic hypermutation in antigen-reactive B cells. NK cells restrict follicular helper T cell (TFH ) and GC B cell frequencies and titers of antigen-specific immunoglobulin after administration of alum-adjuvanted hapten-protein conjugate vaccines. This inhibition is perforin dependent, suggesting that NK cells kill one or more cells critical for GC development...
September 25, 2018: Cell Reports
John L Snider, Nuengsap Thangthong, Cristiane Pilon, Gurpreet Virk, Viktor Tishchenko
Vigorous seedling growth in cotton is desirable because it minimizes the negative impact of multiple early season stresses, and seedling vigor can be impacted by early season growth temperature or cultivar. OJIP fluorescence provides rapid information on a broad range of photosynthetic component processes and may be a useful surrogate for seeding vigor, but this possibility has not been evaluated previously in cotton. To this end, a controlled environment study was conducted with six cultivars selected based on seed characteristics that are widely indicative of vigor and under two growth temperature regimes (sub-optimal = 20/15 °C day/night temperature; optimal = 30/20 °C) for the first two weeks after seed germination...
November 2018: Plant Physiology and Biochemistry: PPB
Shuang Song, Patrick D Matthias
Germinal centers (GCs) are essential structures of the humoral immune response, which form in the periphery in response to T cell dependent antigens. During the GC reaction, B cells undergo critical differentiation steps, which ultimately lead to the generation of antibodies with altered effector function and higher affinity for the selected antigen. Remarkably, many of the B cell tumors have their origin in the GCs; thus, understanding how the formation of these structures is regulated or deregulated is of high medical importance...
2018: Frontiers in Immunology
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