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Isotype class switching

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...
September 6, 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 centers (GCs) promote humoral immunity and vaccine efficacy. In GCs, antigen (Ag)-activated B lymphocytes proliferate, are selected for high affinity antibody (Ab), promote Ab class switching, and yield B cell memory1,2. Whereas the cytokine milieu has long been known to regulate effector functions that include the choice of immunoglobulin class 3,4, both cell-autonomous5 and extrinsic6,7 metabolic programming have emerged as modulators of T cell-mediated immunity8. We now show that GC light zones are hypoxic and low oxygen (pO2) 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
Yasushi Hara, Yasuyuki Tashiro, Akikazu Murakami, Miyuki Nishimura, Takeyuki Shimizu, Masato Kubo, Peter D Burrows, Takachika Azuma
During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42...
December 2015: Molecular Immunology
Zhangguo Chen, Andrew Getahun, Xiaomi Chen, Yonatan Dollin, John C Cambier, Jing H Wang
Class switch recombination (CSR) generates isotype-switched Abs with distinct effector functions. B cells express phosphatase and tensin homolog (PTEN) and multiple isoforms of class IA PI3K catalytic subunits, including p110α and p110δ, whose roles in CSR remain unknown or controversial. In this article, we demonstrate a direct effect of PTEN on CSR signaling by acute deletion of Pten specifically in mature B cells, thereby excluding the developmental impact of Pten deletion. We show that mature B cell-specific PTEN overexpression enhances CSR...
December 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Konstantinos Tsioris, Namita T Gupta, Adebola O Ogunniyi, Ross M Zimnisky, Feng Qian, Yi Yao, Xiaomei Wang, Joel N H Stern, Raj Chari, Adrian W Briggs, Christopher R Clouser, Francois Vigneault, George M Church, Melissa N Garcia, Kristy O Murray, Ruth R Montgomery, Steven H Kleinstein, J Christopher Love
West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis...
December 2015: Integrative Biology: Quantitative Biosciences From Nano to Macro
Lisa A Cummings, Brooke L Deatherage, Brad T Cookson
The interaction betweenSalmonella and its host is complex and dynamic: the host mounts an immune defense against the pathogen, which in turn acts to reduce, evade, or exploit these responses to successfully colonize the host. Although the exact mechanisms mediating protective immunity are poorly understood, it is known that T cells are a critical component of immunity to Salmonella infection, and a robust T-cell response is required for both clearance of primary infection and resistance to subsequent challenge...
August 2009: EcoSal Plus
Melinda Herbáth, Krisztián Papp, Anna Erdei, József Prechl
Natural and synthetic nucleic acids are known to exert immunomodulatory properties. Notably, nucleic acids are known to modulate immune function via several different pathways and various cell types, necessitating a complex interpretation of their effects. In this study we set out to compare the effects of a CpG motif containing oligodeoxynucleotide (ODN) with those of a control and an inhibitory non-CpG ODN during cognate B cell-T cell interactions. We employed an antigen presentation system using splenocytes from TCR transgenic DO11...
2015: Journal of Immunology Research
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