An Overview of B Cells – from Discovery to Therapy Mini Review
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Intrinsic and Extrinsic Mechanisms for B-Cell Lymphoma Development and Progression Studied by Global Gene Expression Profiling
From the Department of Laboratory Medicine Karolinska Institutet, Stockholm, Sweden INTRINSIC AND EXTRINSIC MECHANISMS FOR B-CELL LYMPHOMA DEVELOPMENT AND PROGRESSION STUDIED BY GLOBAL GENE EXPRESSION PROFILING Gustav Arvidsson Stockholm 2019 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Universitetsservice US-AB © Gustav Arvidsson, 2019 ISBN 978-91-7831-518-5 Intrinsic and extrinsic mechanisms for B-cell lymphoma development and progression studied by global gene expression profiling THESIS FOR DOCTORAL DEGREE (Ph.D.) By Gustav Arvidsson Principal Supervisor: Opponent: Professor Anthony Wright Professor Mikael Sigvardsson Karolinska Institutet Lund University Department of Laboratory Medicine Department of Laboratory Medicine Clinical Research Center Division of Molecular Haematology Co-supervisor: Examination Board: Professor Birgitta Sander Professor Lars-Gunnar Larsson Karolinska Institutet Karolinska Institutet Department of Laboratory Medicine Department of Microbiology, Tumor and Cell Division of Pathology Biology Associate Professor Ingrid Glimelius Uppsala University Department of Immunology, Genetics and Pathology Associate Professor Fredrik Öberg Uppsala University Department of Immunology, Genetics and Pathology For E and E ABSTRACT Mantle cell lymphoma (MCL) is a rare hematopoietic malignancy characterized by frequent relapses and poor survival, partly due to minimal residual disease, whereby a subset of malignant cells, harbored in protective niches, survive treatment. In vitro and ex vivo experiments have shown that MCL cells can be rescued from apoptosis through interactions with non-malignant cells such as stromal cells. The present thesis investigates the effect that extrinsic microenvironmental interactions may exert on MCL cells and discuss the presumptive role of these as well as intrinsic mechanisms in the development and progression of lymphomas. -
SAHLGRENSKA AKADEMIN Thymic Studies
Göteborg, 2019 Thymic studies Investigations into the effects of childhood thymectomy, and characterization of thymic B cells and Hassall's corpuscles Akademisk avhandling Som för avläggande av medicine doktorsexamen vid Sahlgrenska akademin, Göteborgs universitet kommer att offentligen försvaras i föreläsningssalen våning 3, Guldhedsgatan 10A, Göteborg Tisdagen den 14e maj, klockan 13.00 av Christina Lundqvist Fakultetsopponent: Professor Ludger Klein Ludwig-Maximilians-Universität, Tyskland Avhandlingen baseras på följande delarbeten I. Gudmundsdottir J*, Lundqvist C*, Ijspeert H, van der Slik E, Óskarsdóttir S, Lindgren S, Lundberg V, Berglund M, Lingman-Framme J, Telemo E, van der Burg M, Ekwall O. T-cell receptor sequencing reveals decreased diversity 18 years after early thymectomy. J Allergy Clin Immunol. 2017 Dec;140(6):1743- 1746.e7. doi: 10.1016/j.jaci.2017.08.002. Epub 2017 Sep 1. * These authors contributed equally to this work. II. Lundqvist C*, Camponeschi A*, Visentini M, Telemo E, Ekwall O‡, Mårtensson IL‡. Switched CD21-/low B cells with an antigen-presenting phenotype in the infant thymus. J Allergy Clin Immunol. 2018 Nov 30. pii: S0091-6749(18)31721- 4. doi: 10.1016/j.jaci.2018.11.019. * These authors contributed equally to this work. ‡ These authors contributed equally to this work. III. Lundqvist C, Lindgren S, Cheuk S, Lundberg V, Berglund M, Thörn K, Telemo E, Ekwall O. Characterization of Hassall's corpuscles in the human thymus. Manuscript SAHLGRENSKA AKADEMIN INSTITUTIONEN FÖR MEDICIN Göteborg, 2019 Thymic studies Investigations into the effects of childhood thymectomy, and characterization of thymic B cells and Hassall's corpuscles Christina Lundqvist Avdelningen för reumatologi och inflammationsforskning, Institutionen för medicin, Sahlgrenska akademin, Göteborgs universitet Abstract This thesis focuses on the human thymus, a primary lymphoid organ responsible for the maturation of T cells. -
Hemolysin from Escherichia Coli Uses Endogenous Amplification Through P2X Receptor Activation to Induce Hemolysis
␣-Hemolysin from Escherichia coli uses endogenous amplification through P2X receptor activation to induce hemolysis Marianne Skalsa, Niklas R. Jorgensenb, Jens Leipzigera, and Helle A. Praetoriusa,1 aDepartment of Physiology and Biophysics, Water and Salt Research Center, Aarhus University, Ole Worms Alle 1160, 8000 Aarhus C, Denmark; and bDepartment for Clinical Biochemistry, Roskilde Hospital, Koegevej 3-7, 4000 Roskilde, Denmark Edited by Sucharit Bhakdi, University of Mainz, Mainz, Germany, and accepted by the Editorial Board January 6, 2009 (received for review July 22, 2008) Escherichia coli is the dominant facultative bacterium in the normal and are referred to as P2X1–7. All P2X receptors are permeable to intestinal flora. E. coli is, however, also responsible for the majority small monovalent cations and some have significant calcium per- of serious extraintestinal infections. There are distinct serotypical meability (11). Here we show that human, murine, and equine differences between facultative and invasive E. coli strains. Inva- erythrocytes use a combination of P2X1 and P2X7 receptor acti- sive strains frequently produce virulence factors such as ␣-hemolysin vation for full HlyA-induced hemolysis to occur. This is particularly (HlyA), which causes hemolysis by forming pores in the erythrocyte interesting, as prolonged stimulation of P2X7 receptors are known membrane. The present study reveals that this pore formation to increase the plasma membrane permeability to an extent that triggers purinergic receptor activation to mediate the full hemo- eventually leads to lysis of certain cells (12). In macrophages it has lytic action. Non-selective ATP-receptor (P2) antagonists (PPADS, been shown that pannexin1, a recently discovered pore-forming suramin) and ATP scavengers (apyrase, hexokinase) concentration protein, is required for this increment in permeability (12, 13). -
Our Immune System (Children's Book)
OurOur ImmuneImmune SystemSystem A story for children with primary immunodeficiency diseases Written by IMMUNE DEFICIENCY Sara LeBien FOUNDATION A note from the author The purpose of this book is to help young children who are immune deficient to better understand their immune system. What is a “B-cell,” a “T-cell,” an “immunoglobulin” or “IgG”? They hear doctors use these words, but what do they mean? With cheerful illustrations, Our Immune System explains how a normal immune system works and what treatments may be necessary when the system is deficient. In this second edition, a description of a new treatment has been included. I hope this book will enable these children and their families to explore together the immune system, and that it will help alleviate any confusion or fears they may have. Sara LeBien This book contains general medical information which cannot be applied safely to any individual case. Medical knowledge and practice can change rapidly. Therefore, this book should not be used as a substitute for professional medical advice. SECOND EDITION COPYRIGHT 1990, 2007 IMMUNE DEFICIENCY FOUNDATION Copyright 2007 by Immune Deficiency Foundation, USA. Readers may redistribute this article to other individuals for non-commercial use, provided that the text, html codes, and this notice remain intact and unaltered in any way. Our Immune System may not be resold, reprinted or redistributed for compensation of any kind without prior written permission from Immune Deficiency Foundation. If you have any questions about permission, please contact: Immune Deficiency Foundation, 40 West Chesapeake Avenue, Suite 308, Towson, MD 21204, USA; or by telephone at 1-800-296-4433. -
Disposal of Toxin Heptamers by Extracellular Vesicle Formation and Lysosomal Degradation
toxins Article Major Determinants of Airway Epithelial Cell Sensitivity to S. aureus Alpha-Toxin: Disposal of Toxin Heptamers by Extracellular Vesicle Formation and Lysosomal Degradation Nils Möller 1,* , Sabine Ziesemer 1, Christian Hentschker 2, Uwe Völker 2 and Jan-Peter Hildebrandt 1 1 Animal Physiology and Biochemistry, University of Greifswald, Felix Hausdorff-Strasse 1, D-17489 Greifswald, Germany; [email protected] (S.Z.); [email protected] (J.-P.H.) 2 Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Felix Hausdorff-Strasse 8, D-17475 Greifswald, Germany; [email protected] (C.H.); [email protected] (U.V.) * Correspondence: [email protected] Abstract: Alpha-toxin is a major virulence factor of Staphylococcus aureus. Monomer binding to host cell membranes results in the formation of heptameric transmembrane pores. Among human model airway epithelial cell lines, A549 cells were most sensitive toward the toxin followed by 16HBE14o- and S9 cells. In this study we investigated the processes of internalization of pore-containing plasma membrane areas as well as potential pathways for heptamer degradation (lysosomal, proteasomal) or disposal (formation of exosomes/micro-vesicles). The abundance of toxin heptamers upon applying an alpha-toxin pulse to the cells declined both in extracts of whole cells and of cellular membranes of Citation: Möller, N.; Ziesemer, S.; S9 cells, but not in those of 16HBE14o- or A549 cells. Comparisons of heptamer degradation rates un- Hentschker, C.; Völker, U.; der inhibition of lysosomal or proteasomal degradation revealed that an important route of heptamer Hildebrandt, J.-P. -
B-Cell Reconstitution Recapitulates B-Cell Lymphopoiesis Following Haploidentical BM Transplantation and Post-Transplant CY
Bone Marrow Transplantation (2015) 50, 317–319 © 2015 Macmillan Publishers Limited All rights reserved 0268-3369/15 www.nature.com/bmt LETTER TO THE EDITOR B-cell reconstitution recapitulates B-cell lymphopoiesis following haploidentical BM transplantation and post-transplant CY Bone Marrow Transplantation (2015) 50, 317–319; doi:10.1038/ From week 9, the proportion of transitional B cells progressively bmt.2014.266; published online 24 November 2014 decreased (not shown), whereas that of mature B cells increased (Figure 1d). To further evaluate the differentiation of mature cells, we included markers of naivety (IgM and IgD) and memory (IgG) in The treatment of many hematological diseases benefits from our polychromatic panel. At week 9, when a sufficient proportion myeloablative or non-myeloablative conditioning regimens of cells were available for the analysis, B cells were mostly naive followed by SCT or BMT. HLA-matched donors are preferred but and remained so for 26 weeks after haploBMT (Figure 1d). Despite not always available. Instead, haploidentical donors can be rapidly low, the proportion of memory B cells reached levels similar to identified. Unmanipulated haploidentical BMT (haploBMT) with that of marrow donors (Supplementary Figure 1D). non-myeloablative conditioning and post-transplant Cy has been To further investigate the steps of B-cell maturation, we developed to provide a universal source of BM donors.1 Cy, analyzed CD5, a regulator of B-cell activation, and CD21, a which depletes proliferating/allogeneic cells, prevents GVHD.1 component of the B-cell coreceptor complex, on transitional B Importantly, the infection-related mortality was remarkably low, cells. These surface markers characterize different stages of 5,6 5,6 suggesting effective immune reconstitution.1,2 However, a transitional B-cell development. -
B Cell Subsets in Autoimmune Disease B Cell Subsetsb Cell in Autoimmune Disease
Thesis for doctoral degree (Ph.D.) 2018 Thesis for doctoral degree (Ph.D.) 2018 (Ph.D.) degree doctoral Thesis for B cell subsets in autoimmune disease B cell subsets in autoimmune disease B cell in autoimmune subsets Katrin Habir Katrin Habir From DEPARTMENT OF MEDICINE Karolinska Institutet, Stockholm, Sweden B CELL SUBSETS IN AUTOIMMUNE DISEASE Katrin Habir Stockholm 2018 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Printed by Eprint AB 2018 © Katrin Habir, 2018 ISBN 978-91-7676-900-3 B CELL SUBSETS IN AUTOIMMUNE DISEASE THESIS FOR DOCTORAL DEGREE (Ph.D.) AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i CMM Lecture Hall, L8:00, Center for Molecular Medicine (CMM), Karolinska Universitetssjukhuset, Solna. Friday February 2nd 2018 at 09.00 by Katrin Habir Principal Supervisor: Opponent: Dr. Stephen Malin Associate Professor Bengt Johansson Lindbom Karolinska Institutet Lunds Universitet Department of Medicine Department of Experimental Medical Science Division of Cardiovascular Medicine Division of Adaptive Immunity Co-supervisors: Examination Board: Professor Gunilla Karlsson Hedestam Professor Birgitta Heyman Karolinska Institutet Uppsala Universitet Department of Microbiology, Tumor and Cell Department of Medical Biochemistry and Biology Microbiology Division of Microbiology-Immunology Professor Dan Grandér Karolinska Institutet Associate Professor Lisa Westerberg Department of Oncology-Pathology Karolinska Institutet Department of Microbiology, Tumor and Cell Biology Associate Professor Angela Silveira Karolinska Institutet Department of Medicine Division of Cardiovascular Medicine “We still do not know one thousandth of one percent of what nature has revealed to us.” Albert Einstein THIS THESIS IS DEDICATED TO MY BELOVED ONES ABSTRACT B lymphocytes are a type of white blood cells, belonging to the adaptive arm of the immune system and involved in creating immunological memory. -
Transport Proteins Promoting Escherichia Coli Pathogenesis
Microbial Pathogenesis 71-72 (2014) 41e55 Contents lists available at ScienceDirect Microbial Pathogenesis journal homepage: www.elsevier.com/locate/micpath Transport proteins promoting Escherichia coli pathogenesis Fengyi Tang 1, Milton H. Saier Jr. * Department of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0116, USA article info abstract Article history: Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide Received 26 November 2013 annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, Received in revised form gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and 19 March 2014 compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related Accepted 20 March 2014 to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell Available online 18 April 2014 surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity Keywords: Escherichia coli secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex re- fi Pathogenesis ceptors and high-af nity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar Transporters encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in Toxins K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, Iron acquisition different from those of extracellular pathogens. The results presented in this report provide information Intra vs. -
Defining Natural Antibodies
PERSPECTIVE published: 26 July 2017 doi: 10.3389/fimmu.2017.00872 Defining Natural Antibodies Nichol E. Holodick1*, Nely Rodríguez-Zhurbenko2 and Ana María Hernández2* 1 Department of Biomedical Sciences, Center for Immunobiology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI, United States, 2 Natural Antibodies Group, Tumor Immunology Division, Center of Molecular Immunology, Havana, Cuba The traditional definition of natural antibodies (NAbs) states that these antibodies are present prior to the body encountering cognate antigen, providing a first line of defense against infection thereby, allowing time for a specific antibody response to be mounted. The literature has a seemingly common definition of NAbs; however, as our knowledge of antibodies and B cells is refined, re-evaluation of the common definition of NAbs may be required. Defining NAbs becomes important as the function of NAb production is used to define B cell subsets (1) and as these important molecules are shown to play numerous roles in the immune system (Figure 1). Herein, we aim to briefly summarize our current knowledge of NAbs in the context of initiating a discussion within the field of how such an important and multifaceted group of molecules should be defined. Edited by: Keywords: natural antibody, antibodies, natural antibody repertoire, B-1 cells, B cell subsets, B cells Harry W. Schroeder, University of Alabama at Birmingham, United States NATURAL ANTIBODY (NAb) PRODUCING CELLS Reviewed by: Andre M. Vale, Both murine and human NAbs have been discussed in detail since the late 1960s (2, 3); however, Federal University of Rio cells producing NAbs were not identified until 1983 in the murine system (4, 5). -
IHC) Outreach Services
IIImmunohistochemistry (IHC) Outreach Services Note type of fixative used if not neutral buffered formalin. Note type of tissue/specimen Unless specified otherwise, positive and negative controls react satisfactorily. Available Chromogen – All markers have been validated with 3,3’-Diaminobenzidine Tetrahydrochloride (DAB) which results in a brown/black precipitate. DAB is the routine chromogen. In addition, some markers have also been validated using the Fast Red (RED), which results in a red precipitate. If available with both chromogens and one is not selected, the def ault will be the DAB chromogen. Antibody Common Applications St aining Charac teristi cs Actin (muscl e sp eci fic ) Smoo th, ske letal & ca rdiac musc le Cytoplasm ic Actin (smoo th muscle ) Smoo th muscl e an d myoep itheli al cel ls Cytoplasm ic and memb rane ALK Pr otein ALK1 posi tive lymp homa s Cytoplasm ic and/or nuclea r Alph a-1-Antitr ypsi n Demo nstr ates A-1-AT in liver Cytoplasm ic (A-1-AT) Bcl-2 Oncop rotein Foll icula r lymph oma an d so ft tiss ue Cytoplasm ic tumors Bcl-6 Foll icula r lymph oma Nucl ear Ber-EP 4, Epithelia l Antige n Aden oca rcin oma vs. meso the liom a Memb rane and cytoplasm ic. The and epithelial tumors membrane staining is preferentially basolateral. Beta-Amyloid Pos t mo rt em dia gnos is of demen tia E xtr acel lular de pos ition (am yloid plaques), vascular deposition (amyloid angiopathy) BRS T-3, (B72.3) Aden oca rcin oma vs. -
Self-Reactive B Cells in the GALT Are Actively Curtailed to Prevent Gut Inflammation
Self-reactive B cells in the GALT are actively curtailed to prevent gut inflammation Ashima Shukla, … , John R. Apgar, Robert C. Rickert JCI Insight. 2019;4(16):e130621. https://doi.org/10.1172/jci.insight.130621. Research Article Immunology Inflammation Immune homeostasis in the gut-associated lymphoid tissues (GALT) is critical to prevent the development of inadvertent pathologies. B cells, as the producers of antibodies and cytokines, play an important role in maintaining the GALT homeostasis. However, the mechanism by which B cells specifically direct their responses toward non-self-antigens and become ignorant to self-antigens in the GALT is not known. Therefore, we developed what we believe to be a novel mouse model by expressing duck egg lysozyme (DEL) in gut epithelial cells in presence of HEL-reactive B cells. Notably, we observed a transient activation and rapid deletion of self-reactive B cells in Peyer’s patches and mesenteric lymph nodes upon self-antigen exposure. The survival of self-reactive B cells upon exposure to their self-antigen was partially rescued by blocking receptor editing but could be completely rescued by stronger survival signal, such as ectopic expression of BCL2. Importantly, rescuing the self-reactive B cells promoted production of autoantibodies and gut inflammation. Mechanistically, we identify a specific activation of TGF-β signaling in self-reactive B cells in the gut and a critical role of this pathway in maintaining peripheral tolerance. Collectively, our studies describe functional consequences and the fate of self-reactive B cells in GALT and provide potentially novel mechanistic insights governing self-tolerance of B cells in the gut. -
Med-Pathway Zoom Workshop
MCAT Immunology Dr. Phillip Carpenter medpathwaymcat Med-pathway AAMC MCAT Content Outline: Immunology Category 1A: Structure/Function of Proteins/AA Immune System Category 3B: Organ Systems Innate vs. Adaptive Immunity T and B Lymphocytes Macrophages & Phagocytes Tissue-Bone marrow, Spleen, Thymus, Lymph nodes Antigen and Antibody Antigen Presentation Clonal Selection Antigen-Antibody recognition Structure of antibody molecule Self vs. Non-self, Autoimmune Diseases Major Histocompatibility Complex Lab Techniques: ELISA & Western Blotting Hematopoiesis Creates Immune Cells Self vs. Non-self Innate vs Adaptive Innate Immunity Physical Barriers: Skin, mucous membranes, pH Inflammatory mediators: Complement, Cytokines, Prostaglandins Cellular Components: Phagocytes-Neutrophils, Eosinophils, Basophils, Mast Cells Antigen Presenting Cells-Monocytes, Macrophages, Dendritic Cells Adaptive (Acquired) Immunity Composed of B and T lymphocytes: Activated by Innate Immunity B cells: Express B cell receptor and secrete antibodies as plasma cells T cells: Mature in thymus, express TCR surface receptor; Activated by Antigen Presenting Cells (APCs) Direct Immune response (The Ringleaders of immune system) Major Lymphoid Organs TYPE SITE FUNCTION Fetal production of Liver 1° lymphoid cells Hematopoietic production of 1° Bone marrow myeloid and lymphoid cells Receives bone marrow T 1° Thymus cells; site where self is selected from non-self Lymph nodes 2° Sites of antigen activation Spleen of lymphocytes; clearance Macrophages (Sentinel Cells) Pattern Recognition