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IgA class switch

Makoto Irahara, Wakako Shinahara, Mayumi Sugimoto, Yukiko Ogawa, Keiji Shitsukawa, Kenji Kubota, Limin Yang, Yukihiro Ohya, Hirohisa Saito, Shoji Kagami, Kokichi Arisawa, Hiroshi Kido
INTRODUCTION: Allergen-specific immunoglobulin isotype formation associated with immunoglobulin class-switching during the lactation period is the immunological background for food allergy in infants. We analyzed the serial changes in the production of feeding type-related egg- and milk-specific immunoglobulin isotypes from birth to 6 months of age with or without eczema in 84 infants. METHODS: Allergen-specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, IgA, and IgE levels of hen's egg and bovine milk were measured in cord blood and blood samples from infants at 2, 4, and 6 months of age by the densely carboxylated protein microarray...
March 11, 2019: Immunity, Inflammation and Disease
Felipe Melo-Gonzalez, Hana Kammoun, Elza Evren, Emma E Dutton, Markella Papadopoulou, Barry M Bradford, Ceylan Tanes, Fahmina Fardus-Reid, Jonathan R Swann, Kyle Bittinger, Neil A Mabbott, Bruce A Vallance, Tim Willinger, David R Withers, Matthew R Hepworth
Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell-dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell-dependent IgA responses remain incompletely understood...
February 27, 2019: Journal of Experimental Medicine
Barbara Frossi, Giulia Antoniali, Kefei Yu, Nahid Akhtar, Mark H Kaplan, Mark R Kelley, Gianluca Tell, Carlo E M Pucillo
The base excision repair (BER) pathway is an important DNA repair pathway and is essential for immune responses. In fact, it regulates both the antigen-stimulated somatic hypermutation (SHM) process and plays a central function in the process of class switch recombination (CSR). For both processes, a central role for apurinic/apyrimidinic endonuclease 1 (APE1) has been demonstrated. APE1 acts also as a master regulator of gene expression through its redox activity. APE1's redox activity stimulates the DNA-binding activity of several transcription factors, including NF-kB and a few others involved in inflammation and in immune responses...
January 31, 2019: Journal of Biological Chemistry
Trisha A Rettig, Bailey A Bye, Nina C Nishiyama, Savannah Hlavacek, Claire Ward, Michael J Pecaut, Stephen K Chapes
Spaceflight affects the immune system, but the effects on the antibody repertoire, responsible for humoral immunity, has not been well explored. In particular, the complex gene assembly and expression process; including mutations, might make this process vulnerable. Complementarity determining region 3 (CDR3), composed of parts of the V-(D-)J-gene segments, is very important for antigen binding and can be used as an important measure of variability. Skeletal unloading, and the physiological effects of it, parallel many impacts of space flight...
2019: PloS One
Daniel Appelgren, Per Eriksson, Jan Ernerudh, Mårten Segelmark
In mice, B1 and marginal zone (MZ) B-cells play an important role in prevention of autoimmunity through production of regulatory cytokines and natural antibodies. There is limited knowledge about the human counterparts of these cells. We therefore investigated functions of MZ-like B-cells and the frequency of circulating MZ-like and B1-like B-cells in healthy controls (HC), as well as in patients with autoimmune vasculitis to learn more about the role of these cells in autoimmune disease. After stimulation with CpG oligodeoxynucleotides (ODN) of class B in vitro , MZ-like B-cells were the main producers of IgM whereas switched memory B-cells primarily produced IgG and IgA...
2018: Frontiers in Immunology
Jeffrey L Curtis
No abstract text is available yet for this article.
October 23, 2018: American Journal of Respiratory and Critical Care Medicine
Rekha D Jhamnani, Cristiane J Nunes-Santos, Jenna Bergerson, Sergio D Rosenzweig
Antibody production and function represent an essential part of the immune response, particularly in fighting bacterial and viral infections. Multiple immunological phenotypes can result in dysregulation of the immune system humoral compartment, including class-switch recombination (CSR) defects associated with hyper-IgM (HIGM) syndromes. The CSR/HIGM syndromes are defined by the presence of normal or elevated plasma IgM levels in the context of low levels of switched IgG, IgA, and IgE isotypes. Recently described autosomal dominant gain-of-function (GOF) mutations in PIK3CD and PIK3R1 cause combined immunodeficiencies that can also present as CSR/HIGM defects...
2018: Frontiers in Immunology
Hye-Ju Han, Young-Saeng Jang, Goo-Young Seo, Sung-Gyoo Park, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Geun-Shik Lee, Pyeung-Hyeun Kim
γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ-/- ) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ-/- mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells...
August 2018: Immune Network
Zahra Alizadeh, Marzieh Mazinani, Masoud Houshmand, Leila Shakerian, Maryam Nourizadeh, Zahra Pourpak, Mohammad Reza Fazlollahi
BACKGROUND: Hyper IgM Syndrome (HIGM) is a rare primary immunodeficiency in which impairment of class switching recombination (CSR) and somatic hyper-mutation (SHM) leads to recurrent infections. OBJECTIVES: The aim of this study is to report the clinical and genetic features of six Iranian HIGM patients. METHODS: Six patients, who suspected to have HIGM based on two clinical findings, including recurrent infections and low levels of IgG and IgA and normal or elevated levels of IgM, were entered this study to undergo genetic studies...
August 6, 2018: Immunological Investigations
Victoria K Tesch, Hanna IJspeert, Andrea Raicht, Daniel Rueda, Nerea Dominguez-Pinilla, Luis M Allende, Chrystelle Colas, Thorsten Rosenbaum, Denisa Ilencikova, Hagit N Baris, Michaela H M Nathrath, Manon Suerink, Danuta Januszkiewicz-Lewandowska, Iman Ragab, Amedeo A Azizi, Soeren S Wenzel, Johannes Zschocke, Wolfgang Schwinger, Matthias Kloor, Claudia Blattmann, Laurence Brugieres, Mirjam van der Burg, Katharina Wimmer, Markus G Seidel
Immunoglobulin class-switch recombination (CSR) and somatic hypermutations (SHMs) are prerequisites for antibody and immunoglobulin receptor maturation and adaptive immune diversity. The mismatch repair (MMR) machinery, consisting of homologs of MutSα, MutLα, and MutSβ (MSH2/MSH6, MLH1/PMS2, and MSH2/MSH3, respectively) and other proteins, is involved in CSR, primarily acting as a backup for nonhomologous end-joining repair of activation-induced cytidine deaminase-induced DNA mismatches and, furthermore, in addition to error-prone polymerases, in the repair of SHM-induced DNA breaks...
2018: Frontiers in Immunology
Joana M Santos, Fatima-Zohra Braikia, Chloé Oudinet, Dania Haddad, Caroline Conte, Audrey Dauba, Ahmed Amine Khamlichi
During an adaptive immune response, B cells can change their surface immunoglobulins from IgM to IgG, IgE or IgA through a process called class switch recombination (CSR). Switching is preceded by inducible non-coding germline transcription (GLT) of the selected constant gene(s), which is largely controlled by a super-enhancer called the 3' regulatory region (3'RR). Despite intense efforts, the precise mechanisms that regulate GLT are still elusive. In order to gain additional insights into these mechanisms, we analyzed GLT and CSR in mutant B cells carrying a duplication of the promoter of the α constant gene (Iα) downstream of 3'RR...
June 15, 2018: Scientific Reports
Jacobus Hendricks, Nicolaas A Bos, Frans G M Kroese
The marginal zone (MZ) is largely composed of a unique subpopulation of B cells, the so-called MZ-B cells. At a molecular level, memory B cells are characterized by the presence of somatically mutated IGV genes. The earliest studies in the rat have documented the presence of hapten-specific MZ-B cells after immunization in the MZ. This work later received experimental support demonstrating that the IGHV-Cµ transcripts expressed by phenotypically defined splenic MZ-B cells (defined as CD90neg IgMhigh IgDlow B cells) can carry somatic hypermutation...
2018: Critical Reviews in Immunology
Andri L Lemarquis, Helga K Einarsdottir, Rakel N Kristjansdottir, Ingileif Jonsdottir, Bjorn R Ludviksson
Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells...
2018: Frontiers in Immunology
Lianne J N Kraal, Marieke L Nijland, Kristine L Germar, Dominique L P Baeten, Ineke J M Ten Berge, Cynthia M Fehres
Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints, characterized by the presence of the highly disease-specific anti-citrullinated protein antibodies (ACPA) in approximately 70% of patients. Epstein-Barr virus (EBV) has previously been suggested to be involved in the pathophysiology of RA. However, given the high incidence of EBV in the general population and the difficulty of detecting initial infection, providing a direct link between EBV infection and RA development has remained elusive...
2018: PloS One
Tian Huang, Xifeng Wang, Run Si, Hao Chi, Binyue Han, Haitang Han, Gengsheng Cao, Yaofeng Zhao
Compared with mammals, the bird Ig genetic system relies on gene conversion to create an Ab repertoire, with inversion of the IgA-encoding gene and very few cases of Ig subclass diversification. Although gene conversion has been studied intensively, class-switch recombination, a mechanism by which the IgH C region is exchanged, has rarely been investigated in birds. In this study, based on the published genome of pigeon ( Columba livia ) and high-throughput transcriptome sequencing of immune-related tissues, we identified a transcriptionally forward α gene and found that the pigeon IgH gene locus is arranged as μ-α-υ1-υ2...
June 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Niklas Engels, Jürgen Wienands
The generation of memory B cells (MBCs) that have undergone immunoglobulin class switching from IgM, which dominates primary antibody responses, to other immunoglobulin isoforms is a hallmark of immune memory. Hence, humoral immunological memory is characterized by the presence of serum immunoglobulins of IgG subtypes known as the γ-globulin fraction of blood plasma proteins. These antibodies reflect the antigen experience of B lymphocytes and their repeated triggering. In fact, efficient protection against a previously encountered pathogen is critically linked to the production of pathogen-specific IgG molecules even in those cases where the primary immune response required cellular immunity, for example, T cell-mediated clearance of intracellular pathogens such as viruses...
May 2018: Immunological Reviews
Gholamreza Azizi, Yasser Bagheri, Marzieh Tavakol, Forough Askarimoghaddam, Kumars Porrostami, Hosein Rafiemanesh, Reza Yazdani, Fatemeh Kiaee, Sima Habibi, Kosar Abouhamzeh, Hamed Mohammadi, Mostafa Qorbani, Hassan Abolhassani, Asghar Aghamohammadi
BACKGROUND: Primary antibody deficiency (PAD) comprises a range of diseases from early to late terminal B cells defects and is associated with the various clinical complications. METHODS: A total of 461 patients (311 males and 150 females) with PADs enrolled in the retrospective cohort study and for all patients' demographic information, clinical records and laboratory data were collected to investigate clinical complications. RESULTS: The most prevalent first presentations of immunodeficiency were respiratory tract infections in 63...
2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Caroline H Wallace, Bill X Wu, Mohammad Salem, Ephraim A Ansa-Addo, Alessandra Metelli, Shaoli Sun, Gary Gilkeson, Mark J Shlomchik, Bei Liu, Zihai Li
GARP, a cell surface docking receptor for binding and activating latent TGF-β, is highly expressed by platelets and activated Tregs. While GARP is implicated in immune invasion in cancer, the roles of the GARP-TGF-β axis in systemic autoimmune diseases are unknown. Although B cells do not express GARP at baseline, we found that the GARP-TGF-β complex is induced on activated human and mouse B cells by ligands for multiple TLRs, including TLR4, TLR7, and TLR9. GARP overexpression on B cells inhibited their proliferation, induced IgA class-switching, and dampened T cell-independent antibody production...
April 5, 2018: JCI Insight
Supreet Kumar Mohanty, Deepshi Thakral, Devika Gupta, Prabin Kumar, Dipendra Kumar Mitra
X-linked hyperimmunoglobulin M (HIGM) syndrome may increase the susceptibility of patients to disseminated cryptococcal infections primarily due to CD40L deficiency that causes defective cross talk between T- and B-cells, thus preventing class switching. In HIGM syndrome, serum IgM levels are elevated with severe reduction in serum immunoglobulin G (IgG) and IgA levels. In addition, the expression of CD40L (CD154) on in vitro-activated T-cells is severely reduced or absent. Here, we describe a rare, and perhaps, the first reported case in India of a 3-year-old male child with X-linked HIGM immunodeficiency syndrome who developed disseminated Cryptococcosis...
January 2018: Indian Journal of Pathology & Microbiology
Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop, Andreas Wollenberg
Dupilumab is a new treatment option for patients with moderate-to-severe atopic dermatitis. It blocks IL-4/IL13-signaling and thereby inhibits receptor signaling downstream the JAK-STAT-pathway. Three of the main disease mechanisms of atopic dermatitis are affected by blocking this pathway; the decrease of skin barrier function, the class switch to IgE and the TH2-differentiation. Areas Covered: Dupilumab showed promising results in clinical trials of phase I-III. Clinical outcome parameters such as SCORAD, EASI, IGA and BSA improved with dupilumab...
May 2018: Expert Review of Clinical Pharmacology
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