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Isotype class switching

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
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
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
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
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
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
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
Bart G Jones, Rhiannon R Penkert, Beisi Xu, Yiping Fan, Geoff Neale, Patricia J Gearhart, Julia L Hurwitz
Females and males differ in antibody isotype expression patterns and in immune responses to foreign- and self-antigens. For example, systemic lupus erythematosus is a condition that associates with the production of isotype-skewed anti-self antibodies, and exhibits a 9:1 female:male disease ratio. To explain differences between B cell responses in males and females, we sought to identify direct interactions of the estrogen receptor (ER) with the immunoglobulin heavy chain locus. This effort was encouraged by our previous identification of estrogen response elements (ERE) in heavy chain switch (S) regions...
September 2016: Molecular Immunology
Viqar S Banday, Radha Thyagarajan, Mia Sundström, Kristina Lejon
B cells have an important pathogenic role in the development of type 1 diabetes in the non-obese diabetic (NOD) mouse. We have previously reported that NOD mice display an increased percentage of TACI(high) -expressing B cells compared with C57BL/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI) trait was confirmed using double congenic NOD.B6C1/Idd22 mice. TACI ligation by a proliferation-inducing ligand (APRIL) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch...
November 2016: Immunology
Pedro P Rocha, Ramya Raviram, Yi Fu, JungHyun Kim, Vincent M Luo, Arafat Aljoufi, Emily Swanzey, Alessandra Pasquarella, Alessia Balestrini, Emily R Miraldi, Richard Bonneau, John Petrini, Gunnar Schotta, Jane A Skok
During class switch recombination (CSR), B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH), altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs) in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1...
June 28, 2016: Cell Reports
Piers E M Patten, Gerardo Ferrer, Shih-Shih Chen, Rita Simone, Sonia Marsilio, Xiao-Jie Yan, Zachary Gitto, Chaohui Yuan, Jonathan E Kolitz, Jacqueline Barrientos, Steven L Allen, Kanti R Rai, Thomas MacCarthy, Charles C Chu, Nicholas Chiorazzi
Xenografting primary tumor cells allows modeling of the heterogeneous natures of malignant diseases and the influences of the tissue microenvironment. Here, we demonstrate that xenografting primary chronic lymphocytic leukemia (CLL) B lymphocytes with activated autologous T cells into alymphoid mice results in considerable CLL B cell division and sizable T cell expansion. Nevertheless, most/all CD5(+)CD19(+) cells are eventually lost, due in part to differentiation into antibody-secreting plasmablasts/plasma cells...
April 7, 2016: JCI Insight
Liyu He, Xiaofei Peng, Yinyin Chen, Guoyong Liu, Zhiwen Liu, Jiefu Zhu, Yexin Liu, Hong Liu, Yumei Liang, Fuyou Liu, Lin Sun, Youming Peng
BACKGROUND: Immunoglobulin (Ig) A nephropathy (IgAN) is the xFB01;nding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Increasing evidence suggested that retinoic acid (RA) signaling selectively induces IgA isotype switching and basic leucine zipper transcription factor, ATF-like (BATF) controls the global regulators of class switch recombination (CSR) in lymphocytes. Great effort has been paid to identify whether impaired immune regulation along the 'mucosa-bone marrow (BM) axis' play an important role in the pathogenesis of IgAN...
2016: American Journal of Nephrology
Clemens Wirsum, Cornelia Glaser, Sylvia Gutenberger, Baerbel Keller, Susanne Unger, Reinhard E Voll, Werner Vach, Thomas Ness, Klaus Warnatz
PURPOSE: The aim of this study was to identify characteristics of hypogammaglobulinemia secondary to glucocorticoid therapy and their value in the differential diagnosis to primary forms of antibody deficiency. METHODS: We investigated prevalence and character of hypogammaglobulinemia in a cohort of 36 patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) on glucocorticoid therapy in comparison to a gender- and age-matched cohort of hospital controls...
May 2016: Journal of Clinical Immunology
Jacqueline Dekkers, René E M Toes, Tom W J Huizinga, Diane van der Woude
PURPOSE OF REVIEW: This review provides an update on the recent discoveries on the role of anticitrullinated protein antibodies (ACPA) in early rheumatoid arthritis (RA). RECENT FINDINGS: RA is characterized by an immune response against posttranslationally modified proteins, in particular citrullinated proteins. Recent studies have found that the ACPA response matures shortly before clinical disease manifests itself and is characterized by an increase in titre, isotype switching, antigen-recognition profile, and a change in the Fc-glycosylation pattern...
May 2016: Current Opinion in Rheumatology
Armand Garot, Marie Marquet, Alexis Saintamand, Sébastien Bender, Sandrine Le Noir, Pauline Rouaud, Claire Carrion, Zéliha Oruc, Anne-Gaëlle Bébin, Jeanne Moreau, Kevin Lebrigand, Yves Denizot, Frederick W Alt, Michel Cogné, Eric Pinaud
As a master regulator of functional Ig heavy chain (IgH) expression, the IgH 3' regulatory region (3'RR) controls multiple transcription events at various stages of B-cell ontogeny, from newly formed B cells until the ultimate plasma cell stage. The IgH 3'RR plays a pivotal role in early B-cell receptor expression, germ-line transcription preceding class switch recombination, interactions between targeted switch (S) regions, variable region transcription before somatic hypermutation, and antibody heavy chain production, but the functional ranking of its different elements is still inaccurate, especially that of its evolutionarily conserved quasi-palindromic structure...
February 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Egest J Pone
Toll-like receptors (TLRs) are expressed in B lymphocytes and contribute to B-cell activation, antibody responses, and their maturation. TLR stimulation of mouse B cells induces class switch DNA recombination (CSR) to isotypes specified by cytokines, and also induces formation of IgM(+) as well as class-switched plasma cells. B-cell receptor (BCR) signaling, while on its own inducing limited B-cell proliferation and no CSR, can enhance CSR driven by TLRs. Particular synergistic or antagonistic interactions among TLR pathways, BCR, and cytokine signaling can have important consequences for B-cell activation, CSR, and plasma cell formation...
2016: Methods in Molecular Biology
Julia L Hurwitz, Rhiannon R Penkert, Beisi Xu, Yiping Fan, Janet F Partridge, Robert W Maul, Patricia J Gearhart
Vitamin A deficiencies are common throughout the world and have a significant negative influence on immune protection against viral infections. Mouse models demonstrate that the production of IgA, a first line of defense against viruses at mucosal sites, is inhibited in the context of vitamin A deficiency. In vitro, the addition of vitamin A to activated B cells can enhance IgA expression, but downregulate IgE. Previous reports have demonstrated that vitamin A modifies cytokine patterns, and in so doing may influence antibody isotype expression by an indirect mechanism...
March 2016: Viral Immunology
Laleh Sharifi, Abbas Mirshafiey, Nima Rezaei, Gholamreza Azizi, Kabir Magaji Hamid, Ali Akbar Amirzargar, Mohammad Hossein Asgardoon, Asghar Aghamohammadi
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immune deficiency and is characterized by hypogammaglobulinemia, defect in specific antibody response and increased susceptibility to recurrent infections, malignancy and autoimmunity. Patients with CVID often have defects in post-antigenic B-cell differentiation, with fewer memory B cells and impaired isotype switching. Toll-like receptors (TLRs) are expressed on various immune cells as key elements of innate and adaptive immunity...
February 2016: Expert Review of Clinical Immunology
Kate Senger, Jason Hackney, Jian Payandeh, Ali A Zarrin
The humoral or antibody-mediated immune response in vertebrates has evolved to respond to diverse antigenic challenges in various anatomical locations. Diversification of the immunoglobulin heavy chain (IgH) constant region via isotype switching allows for remarkable plasticity in the immune response, including versatile tissue distribution, Fc receptor binding, and complement fixation. This enables antibody molecules to exert various biological functions while maintaining antigen-binding specificity. Different immunoglobulin (Ig) classes include IgM, IgD, IgG, IgE, and IgA, which exist as surface-bound and secreted forms...
2015: Results and Problems in Cell Differentiation
Eva Bengtén, Melanie Wilson
As in mammals, cartilaginous and teleost fishes possess adaptive immune systems based on antigen recognition by immunoglobulins (Ig), T cell receptors (TCR), and major histocompatibility complex molecules (MHC) I and MHC II molecules. Also it is well established that fish B cells and mammalian B cells share many similarities, including Ig gene rearrangements, and production of membrane Ig and secreted Ig forms. This chapter provides an overview of the IgH and IgL chains in cartilaginous and bony fish, including their gene organizations, expression, diversity of their isotypes, and development of the primary repertoire...
2015: Results and Problems in Cell Differentiation
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