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https://www.readbyqxmd.com/read/28690727/-clinical-and-immunological-profile-of-15-moroccan-patients-with-hyper-igm-syndrome
#1
Hind Ouair, Ibtihal Benhsaien, Leila Jeddane, Jalila El Bakkouri, Naima Elhafidi, Noureddine Rada, Jilali Najib, Fatima Ailal, Hanane Salih Alj, Ahmed Aziz Bousfiha
Hyper IgM syndrome is a well known genetic (primary) immunodeficiency disorder which was first described in 1961. It is caused by B lymphocyte deficiency characterized by normal or elevated serum IgM levels and low or zero levels of IgG, IgA, IgE resulting from isotype-switching deficiency. Clinical manifestations are dominated by recurrent infections, especially involving the digestive tube of the ENT sphere and the lungs. This syndrome is caused by B-cell immunoglobulin class switch deficiency and decreased capacity to induce proliferation of T lymphocytes...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28652580/immunological-phenotype-of-the-murine-lrba-knockout
#2
Laura Gámez-Díaz, Julika Neumann, Fiona Jäger, Michele Proietti, Felicitas Felber, Pauline Soulas-Sprauel, Lisa Perruzza, Fabio Grassi, Tamara Kögl, Peter Aichele, Manfred Kilimann, Bodo Grimbacher, Sophie Jung
Biallelic mutations in the human Lipopolysaccharide Responsive Beige-like Anchor (LRBA) gene lead to a primary immunodeficiency known as LRBA deficiency, characterized by a broad range of clinical manifestations including autoimmunity, organomegaly, hypogammaglobulinemia and recurrent infections. Considering the phenotypic heterogeneity in patients and the severity of the disease, our aim was to assess the role of LRBA in immune cells and to understand the underlying pathomechanisms through the study of a Lrba knockout (Lrba(-/-)) mouse model...
June 27, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28617936/t-follicular-regulatory-cells-in-mice-and-men
#3
REVIEW
Ana Raquel Maceiras, Valter R Fonseca, Ana Agua-Doce, Luis Graca
It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal center (GC) reaction where affinity maturation and isotype switching occurs. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously, presenting simultaneously characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression)...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#4
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28607112/cutting-edge-active-tgf-%C3%AE-1-released-from-garp-tgf-%C3%AE-1-complexes-on-the-surface-of-stimulated-human-b-lymphocytes-increases-class-switch-recombination-and-production-of-iga
#5
Olivier Dedobbeleer, Julie Stockis, Bas van der Woning, Pierre G Coulie, Sophie Lucas
Production of active TGF-β is regulated at a posttranslational level and implies release of the mature cytokine dimer from the inactive, latent TGF-β precursor. There are several cell-type specific mechanisms of TGF-β activation. We identified a new mechanism operating on the surface of human regulatory T cells and involving membrane protein GARP, which binds latent TGF-β1. The paracrine activity of regulatory T cell-derived TGF-β1 contributes to immunosuppression and can be inhibited with anti-GARP Abs...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28596550/booster-immunizations-with-dna-plasmids-encoding-her-2-neu-prevent-spontaneous-mammary-cancer-in-her-2-neu-transgenic-mice-over-life-span
#6
Mauro Provinciali, Alessandra Barucca, Fiorenza Orlando, Elisa Pierpaoli
Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours progressively appearing during aging. In this study we evaluated whether booster immunizations (BI) of HER-2/neu transgenic mice with HER-2/neu DNA plasmids every 6 (ECD6), 3 (ECD3), or 1.5 (ECD1.5) months after SI induce a protective immunity that could be maintained over life span...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28574479/r-loops-in-the-regulation-of-antibody-gene-diversification
#7
REVIEW
Rushad Pavri
For nearly three decades, R loops have been closely linked with class switch recombination (CSR), the process that generates antibody isotypes and that occurs via a complex cascade initiated by transcription-coupled mutagenesis in switch recombination sequences. R loops form during transcription of switch recombination sequences in vitro and in vivo, and there is solid evidence that R loops are required for efficient class switching. The classical model of R loops posits that they boost mutation rates by generating stable and long tracts of single-stranded DNA that serve as the substrate for activation induced deaminase (AID), the enzyme that initiates the CSR reaction cascade by co-transcriptionally mutating ssDNA in switch recombination sequences...
June 2, 2017: Genes
https://www.readbyqxmd.com/read/28535205/a-transcriptional-serenaid-the-role-of-noncoding-rnas-in-class-switch-recombination
#8
William T Yewdell, Jayanta Chaudhuri
During an immune response, activated B cells may undergo class switch recombination (CSR), a molecular rearrangement that allows B cells to switch from expressing IgM and IgD to a secondary antibody heavy chain isotype such as IgG, IgA, or IgE. Secondary antibody isotypes provide the adaptive immune system with distinct effector functions to optimally combat various pathogens. CSR occurs between repetitive DNA elements within the immunoglobulin heavy chain (Igh) locus, termed switch (S) regions, and requires the DNA modifying enzyme activation-induced cytidine deaminase (AID)...
May 23, 2017: International Immunology
https://www.readbyqxmd.com/read/28533409/inducible-ctcf-insulator-delays-the-igh-3-regulatory-region-mediated-activation-of-germline-promoters-and-alters-class-switching
#9
Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Zeliha Oruc, Domenico Orlando, Audrey Dauba, Marc Le Bert, Ahmed Amine Khamlichi
Class switch recombination (CSR) plays an important role in adaptive immune response by enabling mature B cells to switch from IgM expression to the expression of downstream isotypes. CSR is preceded by inducible germline (GL) transcription of the constant genes and is controlled by the 3' regulatory region (3'RR) in a stimulus-dependent manner. Why the 3'RR-mediated up-regulation of GL transcription is delayed to the mature B-cell stage is presently unknown. Here we show that mice devoid of an inducible CTCF binding element, located in the α constant gene, display a marked isotype-specific increase of GL transcription in developing and resting splenic B cells and altered CSR in activated B cells...
June 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28520789/antigen-specific-immunoglobulin-variable-region-sequencing-measures-humoral-immune-response-to-vaccination-in-the-equine-neonate
#10
Rebecca L Tallmadge, Steven C Miller, Stephen A Parry, Maria Julia B Felippe
The value of prophylactic neonatal vaccination is challenged by the interference of passively transferred maternal antibodies and immune competence at birth. Taken our previous studies on equine B cell ontogeny, we hypothesized that the equine neonate generates a diverse immunoglobulin repertoire in response to vaccination, independently of circulating maternal antibodies. In this study, equine neonates were vaccinated with 3 doses of keyhole limpet hemocyanin (KLH) or equine influenza vaccine, and humoral immune responses were assessed using antigen-specific serum antibodies and B cell Ig variable region sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28515723/different-somatic-hypermutation-levels-among-antibody-subclasses-disclosed-by-a-new-next-generation-sequencing-based-antibody-repertoire-analysis
#11
Kazutaka Kitaura, Hiroshi Yamashita, Hitomi Ayabe, Tadasu Shini, Takaji Matsutani, Ryuji Suzuki
A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM). Class-switch recombination (CSR) produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS)-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28459542/structure-of-rna-stem-loop-b-from-the-picornavirus-replication-platform
#12
Meghan S Warden, Marco Tonelli, Gabriel Cornilescu, Dong Liu, Lorelei J Hopersberger, Komala Ponniah, Steven M Pascal
The presumptive RNA cloverleaf at the start of the 5'-untranslated region of the picornavirus genome is an essential element in replication. Stem loop B (SLB) of the cloverleaf is a recognition site for the host polyC-binding protein, which initiates a switch from translation to replication. Here we present the solution structure of human rhinovirus isotype 14 SLB using nuclear magnetic resonance spectroscopy. SLB adopts a predominantly A-form helical structure. The stem contains five Watson-Crick base pairs and one wobble base pair and is capped by an eight-nucleotide loop...
May 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/28455167/protective-and-pathogenic-memory-plasma-cells
#13
REVIEW
Bimba F Hoyer, Andreas Radbruch
The immune system can be divided into two major parts: innate and adaptive immunity. Adaptive immunity is characterized by its major cellular players: the B and T cells. B cells will, in the context of an immune reaction, differentiate into plasma cells. These plasma cells produce antibodies, which are secreted. Antibodies are characterized by their specificity against a selected antigen and by their isotype. The isotype changes with the duration or phase of the immune reaction. Early immune reactions are usually characterized by the predominant production of IgM antibodies...
April 25, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28425925/evaluation-of-the-immunomodulatory-properties-of-streptococcus-suis-and-group-b-streptococcus-capsular-polysaccharides-on-the-humoral-response
#14
Cynthia Calzas, Morgan Taillardet, Insaf Salem Fourati, David Roy, Marcelo Gottschalk, Hugo Soudeyns, Thierry Defrance, Mariela Segura
Streptococcus suis and group B Streptococcus (GBS) are encapsulated streptococci causing septicemia and meningitis. Antibodies (Abs) against capsular polysaccharides (CPSs) have a crucial protective role, but the structure/composition of the CPS, including the presence of sialic acid, may interfere with the generation of anti-CPS Ab responses. We investigated the features of the CPS-specific Ab response directed against S. suis serotypes 2 and 14 and GBS serotypes III and V after infection or immunization with purified native or desialylated CPSs in mice...
April 20, 2017: Pathogens
https://www.readbyqxmd.com/read/28422752/t-bet-b-cells-are-induced-by-human-viral-infections-and-dominate-the-hiv-gp140-response
#15
James J Knox, Marcus Buggert, Lela Kardava, Kelly E Seaton, Michael A Eller, David H Canaday, Merlin L Robb, Mario A Ostrowski, Steven G Deeks, Mark K Slifka, Georgia D Tomaras, Susan Moir, M Anthony Moody, Michael R Betts
Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and vaccinia virus vaccinations and also during early acute HIV infection...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28416601/csreport-a-new-computational-tool-designed-for-automatic-analysis-of-class-switch-recombination-junctions-sequenced-by-high-throughput-sequencing
#16
François Boyer, Hend Boutouil, Iman Dalloul, Zeinab Dalloul, Jeanne Cook-Moreau, Jean-Claude Aldigier, Claire Carrion, Bastien Herve, Erwan Scaon, Michel Cogné, Sophie Péron
B cells ensure humoral immune responses due to the production of Ag-specific memory B cells and Ab-secreting plasma cells. In secondary lymphoid organs, Ag-driven B cell activation induces terminal maturation and Ig isotype class switch (class switch recombination [CSR]). CSR creates a virtually unique IgH locus in every B cell clone by intrachromosomal recombination between two switch (S) regions upstream of each C region gene. Amount and structural features of CSR junctions reveal valuable information about the CSR mechanism, and analysis of CSR junctions is useful in basic and clinical research studies of B cell functions...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416599/characterization-of-t-dependent-and-t-independent-b-cell-responses-to-a-virus-like-particle
#17
Wenhua Liao, Zhaolin Hua, Can Liu, Lin Lin, Rui Chen, Baidong Hou
Natural pathogens, such as viruses, often induce T-dependent and T-independent Ab responses. However, the activation and differentiation of Ag-specific B cells under these conditions had not been examined in detail. In this study, we used bacterial phage Qβ-derived virus-like particles (Qβ-VLPs) as an immunogen to examine the T-independent and T-dependent phases of the response in mice. Using Qβ-specific cell labeling and enrichment methods developed in this study, we were able to characterize the rare Ag-specific B cells in detail...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28393124/a-leishmania-murine-model-to-evaluate-the-immunomodulatory-properties-of-pythium-insidiosum-proteins
#18
Tatiana Maria Inêz-Ferreira, Leonel Mendoza, Raquel Vilela, Hélida Monteiro de Andrade, João Paulo Haddad, Fernanda Freire Campos Nunes, Isabela Moreira Gondim, Tânia Mara Pinto Dabés Guimarães, Vicente de Paulo Coelho Peixoto de Toledo
Pythium insidiosum immunomodulatory vaccine (PiV) has been tested in clinical and experimental pythiosis. Previous data showed that P. insidiosum immunogens have the ability to switch the Th2 immune response, normally in place during pythiosis, to a curative Th1 response. Pythiosis cannot be reproduced in experimental rodents with the exception of rabbits, and thus thorough evaluation of PiV´s immunomodulatory properties has been limited by the lack of a compatible inbred mouse model. In this study, we took advantage of the murine BALB/c Leishmania infection model, where infected mice produce a Th2 response, to evaluate the PiV Th2 to Th1 immunomodulatory potential...
March 2017: Heliyon
https://www.readbyqxmd.com/read/28370285/identification-and-characterization-of-a-nationwide-danish-adult-common-variable-immunodeficiency-cohort
#19
Lena Westh, Trine Hyrup Mogensen, Lars Skov Dalgaard, Jens Magnus Bernth Jensen, Terese Katzenstein, Ann-Brit Eg Hansen, Olav Ditlevsen Larsen, Steen Terpling, Thyge Lynghøj Nielsen, Carsten Schade Larsen
In this study we identified all adults living in Denmark diagnosed with common variable immunodeficiency (CVID) and characterized them according to clinical presentation and EUROclass classification. Using a retrospective, cross-sectional design, possible CVID patients were identified in the Danish National Patient Register and Centers in Denmark treating patients with primary immunodeficiencies. The CVID diagnosis was verified by review of medical records. One-hundred-seventy-nine adults with CVID were identified...
April 2, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28333576/epstein-barr-virus-lytic-reactivation-activates-b-cells-polyclonally-and-induces-activation-induced-cytidine-deaminase-expression-a-mechanism-underlying-autoimmunity-and-its-contribution-to-graves-disease
#20
Keiko Nagata, Keisuke Kumata, Yuji Nakayama, Yukio Satoh, Hirotsugu Sugihara, Sayuri Hara, Michiko Matsushita, Satoshi Kuwamoto, Masako Kato, Ichiro Murakami, Kazuhiko Hayashi
Graves' disease is an autoimmune disease that results in and is the most common cause of hyperthyroidism, and the reactivation of persisting Epstein-Barr virus (EBV) in B lymphocytes induces the differentiation of host B cells into plasma cells. We previously reported that some EBV-infected B cells had thyrotropin receptor antibodies (TRAbs) as surface immunoglobulins (Igs), and EBV reactivation induced these TRAb+EBV+ cells to produce TRAbs. EBV reactivation induces Ig production from host B cells. The purpose of the present study was to examine total Ig productions from B cell culture fluids and to detect activation-induced cytidine deaminase (AID), nuclear factor kappa B (NF-κB), and EBV latent membrane protein (LMP) 1 in culture B cells during EBV reactivation induction and then we discussed the mechanisms of EBV reactivation-induced Ig production in relation to autoimmunity...
April 2017: Viral Immunology
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