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Isotype switching

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https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#1
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881702/roles-of-aluminum-hydroxide-and-monophosphoryl-lipid-a-adjuvants-in-overcoming-cd4-t-cell-deficiency-to-induce-isotype-switched-igg-antibody-responses-and-protection-by-t-dependent-influenza-vaccine
#2
Eun-Ju Ko, Young-Tae Lee, Ki-Hye Kim, Youri Lee, Yu-Jin Jung, Min-Chul Kim, Yu-Na Lee, Taeuk Kang, Sang-Moo Kang
Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine. MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell responses, and protection in CD4KO mice, which were comparable to those in WT mice. In contrast, Alum adjuvant effects were dependent on CD4(+) T cells...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27880772/t-cell-production-of-ifn%C3%AE-in-response-to-tlr7-il-12-stimulates-optimal-b-cell-responses-to-viruses
#3
Kira Rubtsova, Anatoly V Rubtsov, Kalani Halemano, Sam X Li, John W Kappler, Mario L Santiago, Philippa Marrack
Knowledge of the processes that underlie IgG subclass switching could inform strategies designed to counteract infections and autoimmunity. Here we show that TLR7 ligands induce subsets of memory CD4 and CD8 T cells to secrete interferon γ (IFNγ) in the absence of antigen receptor stimulation. In turn, TLR ligation and IFNγ cause B cells to express the transcription factor, T-bet, and to switch immunoglobulin production to IgG2a/c. Absence of TLR7 in T cells leads to the impaired T-bet expression in B cells and subsequent inefficient IgG2a isotype switching both in vitro and during the infection with Friend virus in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/27878102/antiretroviral-naive-and-treated-patients-discrepancies-of-b-cell-subsets-during-the-natural-course-of-human-immunodeficiency-virus-type-1-infection
#4
Olga Tsachouridou, Lemonia Skoura, Pantelis Zebekakis, Apostolia Margariti, Adamantini Georgiou, Dimitrios Bougiouklis, Dimitrios Pilalas, Antonios Galanos, Michael Daniilidis, Symeon Metallidis
AIM: To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1 (HIV-1) patients. METHODS: Forty-one antiretroviral naïve and 41 treated HIV-1 patients matched for age and duration of HIV infection were recruited. All clinical, epidemiological and laboratory data were recorded or measured. The different B cell subsets were characterized according to their surface markers: Total B cells (CD19(+)), memory B cells (CD19(+)CD27(+), BMCs), resting BMCs (CD19(+)CD27(+)CD21(high), RM), exhausted BMCs (CD19(+)CD21(low)CD27(-), EM), IgM memory B (CD19(+)CD27(+)IgM(high)), isotype-switched BMCs (CD19(+)CD27(+)IgM(-), ITS) and activated BMCs (CD19(+)CD21(low+)CD27(+), AM) at baseline on week 4 and week 48...
November 12, 2016: World Journal of Virology
https://www.readbyqxmd.com/read/27861512/a-rapid-response-humoral-vaccine-platform-exploiting-pre-existing-non-cognate-populations-of-anti-vaccine-or-anti-viral-cd4-t-helper-cells-to-confirm-b-cell-activation
#5
Thomas Hills, Phillip G Jakeman, Robert C Carlisle, Paul Klenerman, Leonard W Seymour, Ryan Cawood
The need for CD4+ T cell responses to arise de novo following vaccination can limit the speed of B cell responses. Populations of pre-existing vaccine-induced or anti-viral CD4+ T cells recognising distinct antigens could be exploited to overcome this limitation. We hypothesise that liposomal vaccine particles encapsulating epitopes that are recognised, after processing and B cell MHCII presentation, by pre-existing CD4+ T cells will exploit this pre-existing T cell help and result in improved antibody responses to distinct target antigens displayed on the particle surface...
2016: PloS One
https://www.readbyqxmd.com/read/27833954/the-role-of-autoantibodies-in-health-and-disease
#6
Isabela Siloşi, Cristian Adrian Siloşi, Mihail Virgil Boldeanu, Manole Cojocaru, Viorel Biciuşcă, Carmen Silvia Avrămescu, Inimioara Mihaela Cojocaru, Maria Bogdan, Roxana Mihaela FolcuŢi
Serum of healthy individuals contains antibodies that react with self and non-self antigens, generated in absence of external antigen stimulation. These antibodies, called natural antibodies, are particularly IgM isotype, are considered natural autoantibodies (NAA), displaying a moderate affinity for self-antigens. Although incidence of NAA in healthy individuals is not reported, it is established that autoreactive antibodies and B-cells, as well as autoreactive T-cells, are present in healthy persons. The functional abilities of NAA are not clear but is well accepted that they may participate in a variety of activities, such as maintenance of immune homeostasis, regulation of the immune response, resistance to infections, transport and functional modulation of biologically active molecules...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27815447/efficient-culture-of-human-naive-and-memory-b-cells-for-use-as-apcs
#7
Kuei-Ying Su, Akiko Watanabe, Chen-Hao Yeh, Garnett Kelsoe, Masayuki Kuraoka
The ability to culture and expand B cells in vitro has become a useful tool for studying human immunity. A limitation of current methods for human B cell culture is the capacity to support mature B cell proliferation. We developed a culture method to support the efficient activation and proliferation of naive and memory human B cells. This culture supports extensive B cell proliferation, with ∼10(3)-fold increases following 8 d in culture and 10(6)-fold increases when cultures are split and cultured for 8 more days...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27799928/evaluation-of-the-antigen-experienced-b-cell-receptor-repertoire-in-healthy-children-and-adults
#8
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Gertjan J Driessen, Andrew P Stubbs, Mirjam van der Burg
Upon antigen recognition via their B cell receptor (BR), B cells migrate to the germinal center where they undergo somatic hypermutation (SHM) to increase their affinity for the antigen, and class switch recombination (CSR) to change the effector function of the secreted antibodies. These steps are essential to create an antigen-experienced BR repertoire that efficiently protects the body against pathogens. At the same time, the BR repertoire should be selected to protect against responses to self-antigen or harmless antigens...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27780620/variations-of-b-cell-subpopulations-in-peripheral-blood-of-healthy-mexican-population-according-to-age-relevance-for-diagnosis-of-primary-immunodeficiencies
#9
L Berrón-Ruíz, G López-Herrera, C E Ávalos-Martínez, C Valenzuela-Ponce, E Ramírez-SanJuan, G Santoyo-Sánchez, F Mújica Guzmán, F J Espinosa-Rosales, L Santos-Argumedo
BACKGROUND: Peripheral blood B cells include lymphocytes at various stages of differentiation, each with a specific function in the immune response. All these stages show variations in percentage and absolute number throughout human life. The numbers and proportions of B subpopulation are influenced by factors such as gender, age, ethnicity, and lifestyle. This study establishes reference values according to age of peripheral blood B cell subtypes in healthy Mexican population. METHODS: Peripheral blood from healthy new-borns and adults were analysed for total B cell subpopulations, using surface markers such as CD19, IgM, IgD, CD21, CD24, CD27, and CD38, to identify naïve, memory with and without isotype switch, double-negative, transitional, and plasmablast cells...
October 22, 2016: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/27764122/blood-plasma-derived-anti-glycan-antibodies-to-sialylated-and-sulfated-glycans-identify-ovarian-cancer-patients
#10
Tatiana Pochechueva, Alexander Chinarev, Andreas Schoetzau, André Fedier, Nicolai V Bovin, Neville F Hacker, Francis Jacob, Viola Heinzelmann-Schwarz
Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined...
2016: PloS One
https://www.readbyqxmd.com/read/27670591/il-6-promotes-the-differentiation-of-a-subset-of-naive-cd8-t-cells-into-il-21-producing-b-helper-cd8-t-cells
#11
Rui Yang, April R Masters, Karen A Fortner, Devin P Champagne, Natalia Yanguas-Casás, Daniel J Silberger, Casey T Weaver, Laura Haynes, Mercedes Rincon
IL-6 is known to contribute to the differentiation of CD4(+) T cells into different subsets of effector T helper cells. Less is known about the potential of IL-6 in regulating CD8(+) T cell effector function. Here, we identify IL-6 as a master regulator of IL-21 in effector CD8(+) T cells. IL-6 promotes the differentiation of a subset of naive CD8(+) T cells that express IL-6R into a unique population of effector CD8(+) T cells characterized by the production of high levels of IL-21 and low levels of IFN-γ...
October 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27658623/toll-like-receptor-9-activation-rescues-impaired-antibody-response-in-needle-free-intradermal-dna-vaccination
#12
Prabhu S Arunachalam, Ria Mishra, Krithika Badarinath, Deepak Selvam, Sravan K Payeli, Richard R Stout, Udaykumar Ranga
The delivery of plasmid DNA to the skin can target distinct subsets of dermal dendritic cells to confer a superior immune response. The needle-free immunization technology offers a reliable, safe and efficient means to administer intradermal (ID) injections. We report here that the ID injection of DNA vectors using an NF device (NF-ID) elicits a superior cell-mediated immune response, at much lesser DNA dosage, comparable in magnitude to the traditional intramuscular immunization. However, the humoral response is significantly impaired, possibly at the stage of B cell isotype switching...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27658544/activated-gl7-b-cells-are-maintained-within-the-inflamed-cns-in-the-absence-of-follicle-formation-during-viral-encephalomyelitis
#13
Krista D DiSano, Stephen A Stohlman, Cornelia C Bergmann
Central nervous system (CNS) inflammation associated with viral infection and autoimmune disease results in the accumulation of B cells in various differentiation stages. However, the contribution between peripheral and CNS activation remains unclear. During gliatropic coronavirus induced encephalomyelitis, accumulation of protective antibody secreting cells is preceded by infiltration of B cells with a naïve and early differentiation phenotype (Phares et al., 2014). Investigation of the temporal dynamics of B cell activation in draining cervical lymph nodes (CLN) and the CNS revealed that peak CNS infiltration of early activated, unswitched IgD(+) and IgM(+) B cells coincided with polyclonal activation in CLN...
September 19, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27628166/induction-of-robust-immune-responses-in-swine-by-using-a-cocktail-of-adenovirus-vectored-african-swine-fever-virus-antigens
#14
Shehnaz Lokhandwala, Suryakant D Waghela, Jocelyn Bray, Cameron L Martin, Neha Sangewar, Chloe Charendoff, Rashmi Shetti, Clay Ashley, Chang-Hsin Chen, Luc R Berghman, Duncan Mwangi, Paul J Dominowski, Dennis L Foss, Sharath Rai, Shaunak Vora, Lindsay Gabbert, Thomas G Burrage, David Brake, John Neilan, Waithaka Mwangi
The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection...
November 2016: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/27619413/the-concept-of-allergen-associated-molecular-patterns-aamp
#15
REVIEW
Isabella Pali-Schöll, Erika Jensen-Jarolim
For proteins to become allergenic, they need to acquire features enabling them to induce B cell activation and isotype switch to IgE production. Crosslinking of the B-cell receptor (BCR) is the most efficient way to productively activate B-cells. The IgE-crosslinking capability of allergens is equally crucial in the effector phase of immediate type allergy. Antigens, which acquire enhanced crosslinking capacity by oligomerization, aggregation, or the expression of repetitive epitopes may therefore gain allergenic potency...
October 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27609654/heterozygosity-for-transmembrane-activator-and-calcium-modulator-ligand-interactor-a144e-causes-haploinsufficiency-and-pneumococcal-susceptibility-in-mice
#16
Haifa H Jabara, John J Lee, Erin Janssen, Sumana Ullas, Kyriaki Liadaki, Lilit Garibyan, Halli Benson, Tatyana Sannikova, Richard Bram, Lennart Hammarstrom, Anthony C Cruz, Richard Siegel, John Manis, Richard Malley, Raif S Geha
BACKGROUND: The B-cell receptor transmembrane activator and calcium modulator ligand interactor (TACI) is important for T-independent antibody responses. One in 200 blood donors are heterozygous for the TACI A181E mutation. OBJECTIVE: We sought to investigate the effect on B-cell function of TACI A181E heterozygosity in reportedly healthy subjects and of the corresponding TACI A144E mutation in mice. METHODS: Nuclear factor κB (NF-κB) activation was measured by using the luciferase assay in 293T cells cotransfected with wild-type and mutant TACI...
September 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27596815/angioimmunoblastic-t-cell-lymphoma-with-a-clonal-plasma-cell-proliferation-that-underwent-immunoglobulin-isotype-switch-in-the-skin-coinciding-with-cutaneous-disease-progression
#17
Ana E Suárez, M J Artiga, Carlos Santonja, Santiago Montes-Moreno, P De Pablo, Luis Requena, Miguel A Piris, Socorro M Rodríguez-Pinilla
Plasma cell proliferations in specific cutaneous lesions of angioimmunoblastic T-cell lymphoma(AITL) are very uncommon. Here, we report a case of clonal plasma cell proliferation in skin with heavy-chain-immunoglobulin-isotype-switch after cutaneous disease progression. Histopathologically, initial plaque lesions were suggestive of marginal-zone B-cell-lymphoma. Nevertheless, this 77-year-old lady was diagnosed with AITL after the progression of skin lesions from plaques to nodular tumors. A lymph node biopsy confirmed the diagnosis...
December 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27566574/differential-igm-expression-distinguishes-two-types-of-pediatric-burkitt-lymphoma-in-mouse-and-human
#18
Anthony B Eason, Sang-Hoon Sin, Carolina Lin, Blossom Damania, Steven Park, Yuri Fedoriw, Carlos E Bacchi, Dirk P Dittmer
Endemic Burkitt lymphoma (eBL) is primarily a childhood cancer in parts of Africa and Brazil. Classic studies describe eBL as a homogeneous entity based on t(8;14) IgH-Myc translocation and clinical response to cytotoxic therapy. By contrast, sporadic BL (sBL) in Western countries is considered more heterogeneous, and affects both children and adults. It is overrepresented in AIDS patients. Unlike diffuse large B cell lymphoma (DLBCL), molecular subtypes within BL have not been well defined. We find that differential IgM positivity can be used to describe two subtypes of pediatric Burkitt lymphoma both in a high incidence region (Brazil), as well as in a sporadic region (US), suggesting the phenotype is not necessarily geographically isolated...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27540116/clathrin-light-chains-role-in-selective-endocytosis-influences-antibody-isotype-switching
#19
Shuang Wu, Sophia R Majeed, Timothy M Evans, Marine D Camus, Nicole M L Wong, Yvette Schollmeier, Minjong Park, Jagan R Muppidi, Andrea Reboldi, Peter Parham, Jason G Cyster, Frances M Brodsky
Clathrin, a cytosolic protein composed of heavy and light chain subunits, assembles into a vesicle coat, controlling receptor-mediated endocytosis. To establish clathrin light chain (CLC) function in vivo, we engineered mice lacking CLCa, the major CLC isoform in B lymphocytes, generating animals with CLC-deficient B cells. In CLCa-null mice, the germinal centers have fewer B cells, and they are enriched for IgA-producing cells. This enhanced switch to IgA production in the absence of CLCa was attributable to increased transforming growth factor β receptor 2 (TGFβR2) signaling resulting from defective endocytosis...
August 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27501247/germinal-centre-hypoxia-and-regulation-of-antibody-qualities-by-a-hypoxia-response-system
#20
Sung Hoon Cho, Ariel L Raybuck, Kristy Stengel, Mei Wei, Thomas C Beck, Emmanuel Volanakis, James W Thomas, Scott Hiebert, Volker H Haase, Mark R Boothby
Germinal centres (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen-activated B cells proliferate, express high-affinity antibodies, promote antibody class switching, and yield B cell memory. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class, both cell-autonomous and extrinsic metabolic programming have emerged as modulators of T-cell-mediated immunity. Here we show in mice that GC light zones are hypoxic, and that low oxygen tension () alters B cell physiology and function...
August 8, 2016: Nature
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