DOCSLIB.ORG

Survival Function CD23 Expression Independent of Its B Cell Cutting

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Survival Function CD23 Expression Independent of Its B Cell Cutting Cutting Edge: BAFF Regulates CD21/35 and CD23 Expression Independent of Its B Cell Survival Function This information is current as Leonid Gorelik, Anne H. Cutler, Greg Thill, Steven D. of October 4, 2021. Miklasz, Dianna E. Shea, Christine Ambrose, Sarah A. Bixler, Lihe Su, Martin L. Scott and Susan L. Kalled J Immunol 2004; 172:762-766; ; doi: 10.4049/jimmunol.172.2.762 http://www.jimmunol.org/content/172/2/762 Downloaded from References This article cites 20 articles, 9 of which you can access for free at: http://www.jimmunol.org/content/172/2/762.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 4, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts Errata An erratum has been published regarding this article. Please see next page or: /content/172/7/4646.2.full.pdf The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY CUTTING EDGE Cutting Edge: BAFF Regulates CD21/35 and CD23 Expression Independent of Its B Cell Survival Function Leonid Gorelik,1* Anne H. Cutler,1,2* Greg Thill,† Steven D. Miklasz,* Dianna E. Shea,* Christine Ambrose,‡ Sarah A. Bixler,‡ Lihe Su,§ Martin L. Scott,* and Susan L. Kalled3* Herein we demonstrate that B cell-activating factor of the The earliest emigrants from BM to the spleen are transitional TNF family (BAFF), a B cell survival factor, also regulates type 1 (T1) B cells. These cells develop into transitional type 2 CD21/35 and CD23 expression. BAFF blockade in wild- (T2), mature follicular, and marginal zone (MZ) B cells. From type mice down-modulates CD21/35 and CD23 on B cells analysis of BAFF KO mice, it was concluded that B cell devel- while survival remains intact, and BAFF exposure causes opment was blocked at the T1 stage (2, 3). However, it was elevated CD21/35 and CD23 expression. Similar down- shown that while the humoral responses to T-dependent Ags Downloaded from modulation is observed in bcl-2-transgenic mice treated were severely impaired in BAFF KO mice, Ag-specific, class- with a BAFF inhibitor. This is the first evidence that switched Ab was still produced (2, 3). Recently, we showed that BAFF has a function independent of B cell survival. Re- BAFF KO mice form germinal centers (GC) with intact so- ports using CD21/35 and CD23 expression to assess matic hypermutation after Ag challenge (7). These findings splenic B cell subsets in BAFF-null mice concluded a lack suggest that BAFF KO mice possess more differentiated, ma- of B cells beyond the immature stage. Since CD21/35 and ture B cells than originally believed. Therefore, we re-examined http://www.jimmunol.org/ CD23 are inadequate for delineating B cell subpopula- the nature of splenic B cells in BAFF KO mice. During this tions in BAFF-null mice, we used expression of BAFF-R investigation, we found CD21/35 and CD23 expression to be and several B cell markers to identify more mature splenic regulated by BAFF. B cells in these mice. These data broaden our understand- A common method to delineate B cell subsets in the spleen em- ploys surface markers CD21/35 and CD23 since B cells can be ing of BAFF function and correct the view that BAFF-null Ϫ Ϫ ϩ defined as T1, CD21/35 CD23 ; T2, CD21/35highCD23 ; mice lack mature B cells. The Journal of Immunology, low ϩ high Ϫ 2004, 172: 762–766. mature, CD21/35 CD23 ; and MZ, CD21/35 CD23 (8). We and others previously concentrated on CD21/35 and CD23 by guest on October 4, 2021 though the developmental stages of B cell maturation expression to conclude that B cell development in BAFF KO mice 4 was blocked at the T1 stage (2, 3). However, B cell subsets can also from bone marrow (BM) precursors to mature pe- high low/Ϫ ripheral B cells are known, the survival and differen- be defined by IgM and IgD expression: T1, IgM IgD ; T2, A high high low high high low tiation factors required along this pathway have remained elu- IgM IgD ; mature, IgM IgD ; and MZ, IgM IgD sive. B cell-activating factor of the TNF family (BAFF), a TNF (9). Herein we show that BAFF-R, the only BAFF receptor to be family ligand, (also known as BLyS, THANK, TALL-1, and expressed on all peripheral B cells (10), exhibits a differentially reg- zTNF4) (1) was identified as a B cell survival factor and shown ulated pattern of expression on maturing B cells and can be used to to be required for B cell survival since BAFF knockout (KO) identify B cell subsets. Therefore, using expression of IgM, IgD, mice exhibit Ͼ90% loss of peripheral B cells (2, 3). Conversely, BAFF-R, and other B cell markers, we show that BAFF KO mice BAFF-transgenic (Tg) mice, which overexpress BAFF, have have all splenic B cell subsets, but that CD21/35 and CD23 are markedly elevated numbers of peripheral B cells and develop markedly reduced on mature, T2, and MZ B cells. autoimmunity (4–6). Thus, the function of BAFF has signifi- These data led us to hypothesize that BAFF regulates cance in B cell biology as well as disease. BAFF has three known CD21/35 and CD23 expression independently of its survival receptors, BAFF-R (also called BR3), BCMA, and TACI, and function. To test this, we examined B cell CD21/35 and CD23 while BAFF-R binds only to BAFF, TACI and BCMA also bind expression under conditions of BAFF deficiency and excess in APRIL, a related protein (1). vivo and in vitro. We present data that support our hypothesis Departments of *Immunology and Inflammation, †Gene Expression, ‡Gene Discovery, 3 Address correspondence and reprint requests to Dr. Susan L. Kalled, Biogen Idec, and §Protein Chemistry, Biogen Idec Inc., Cambridge Center, Cambridge, MA 02142 Inc., 12 Cambridge Center, Cambridge, MA 02142. E-mail address: [email protected] Received for publication September 11, 2003. Accepted for publication November 11, 2003. 4 Abbreviations used in this paper: BM, bone marrow; BAFF, B cell-activating factor of the TNF family; MZ, marginal zone; T1, transitional type 1; T2, transitional type 2; GC, The costs of publication of this article were defrayed in part by the payment of page germinal center; KO, knockout; Tg, transgenic; hIgG, human IgG; sBAFF, soluble BAFF; charges. This article must therefore be hereby marked advertisement in accordance WT, wild type; MFI, mean fluorescence intensity; FDC, follicular DC; MAdCAM-1, mu- with 18 U.S.C. Section 1734 solely to indicate this fact. cosal addressin cell adhesion molecule 1. 1 L.G. and A.H.C. contributed equally to this work. 2 Current address: Avanir Pharmaceuticals, 11388 Sorrento Valley Road, San Diego, CA 92121. Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 The Journal of Immunology 763 and discuss the implications of diminished CD21/35 and CD23 expression on B cell biology and immunity. Materials and Methods Mice Female BALB/c mice (The Jackson Laboratory, Bar Harbor, ME), BAFF KO, and wild-type (WT) littermates (2) were housed in the Biogen Animal Facility under barrier conditions. Protocols were approved by the Biogen Idec Institu- tional Animal Care and Use Committee. BAFF inhibitor reagents and treatment Human BCMA-Fc (11) and BAFF-R:Fc (12) were described previously. Mice received i.p. 250 ␮g of BAFF-R:Fc, BCMA-Fc, or human IgG (hIgG; Novartis, Basel, Switzerland) as indicated. Flow cytometric analysis FIGURE 1. Splenic B cell subsets in BAFF KO and WT mice. A, Splenocytes were stained with mAbs (BD PharMingen, San Diego, CA) di- Splenocytes from 12-wk-old BAFF KO and WT mice were stained with rected against various markers: IgM-allophycocyanin (11/41), CD21/35-FITC mAbs specific for IgM and IgD for FACS analysis. B cell subsets, T1, T2 (7G6), CD23-biotin (B3B4), B220-FITC (RA3-6B2), CD43-PE (S7), CD22- MZ/T1, and mature (M) are evident in both BAFF KO and WT mice. B, B biotin (Cy34.1), CD24-FITC (M1/69), CD40-FITC (HM40-3), CD19- cell subsets, as defined in A, were examined for CD21/35 and CD23 ex- FITC (1D3), IgD-PE (11-26; Southern Biotechnology Associates, Birming- pression. C, Frozen spleen sections from BAFF KO mice were stained with Downloaded from ham, AL). Anti-BAFF-R-biotin (P1B8 and B9C11) was generated at Biogen. anti-MAdCAM-1 (blue) and anti-IgM (brown) to visualize B cells within Streptavidin-PerCP (BD PharMingen) was used to visualize biotin-labeled the MZ. Arrows point to B cells in the MZ area (magnification, ϫ400). mAbs. Data depicted in A–C are representative of four mice analyzed per group in In vitro assays two separate experiments. Splenocytes from 5- to 6-wk-old BAFF KO and WT mice were prepared under sterile conditions and plated in 24-well plates (Corning, Corning, NY) at 3 ϫ high http://www.jimmunol.org/ 6 ␮ 35 MZ B cells were sparse in BAFF KO mice (Fig.
Load more

Recommended publications
  • Mary Bartlett Bunge 40
    EDITORIAL ADVISORY COMMITTEE Marina Bentivoglio Larry F. Cahill Stanley Finger Duane E. Haines Louise H. Marshall Thomas A. Woolsey Larry R. Squire (Chairperson) The History of Neuroscience in Autobiography VOLUME 4 Edited by Larry R. Squire ELSEVIER ACADEMIC PRESS Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo This book is printed on acid-free paper. (~ Copyright 9 byThe Society for Neuroscience All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier's Science & Technology Rights Department in Oxford, UK: phone: (+44) 1865 843830, fax: (+44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier homepage (http://elsevier.com), by selecting "Customer Support" and then "Obtaining Permissions." Academic Press An imprint of Elsevier 525 B Street, Suite 1900, San Diego, California 92101-4495, USA http ://www.academicpress.com Academic Press 84 Theobald's Road, London WC 1X 8RR, UK http://www.academicpress.com Library of Congress Catalog Card Number: 2003 111249 International Standard Book Number: 0-12-660246-8 PRINTED IN THE UNITED STATES OF AMERICA 04 05 06 07 08 9 8 7 6 5 4 3 2 1 Contents Per Andersen 2 Mary Bartlett Bunge 40 Jan Bures 74 Jean Pierre G. Changeux 116 William Maxwell (Max) Cowan 144 John E. Dowling 210 Oleh Hornykiewicz 240 Andrew F.
    [Show full text]
  • The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target
    Thrombosis and Circulation Open Access Cimmino et al., J Thrombo Cir 2017, 3:1 Review Article Open Access The Two Faces of Thrombosis: Coagulation Cascade and Platelet Aggregation. Are Platelets the Main Therapeutic Target? Giovanni Cimmino*, Salvatore Fischetti and Paolo Golino Department of Cardio-Thoracic and Respiratory Sciences, Section of Cardiology, University of Campania “Luigi Vanvitelli”, Naples, Italy *Corresponding author: Giovanni Cimmino, MD, PhD, Department of Cardio-Thoracic and Respiratory Sciences, Section of Cardiology, University of Campania “Luigi Vanvitelli”, via Leonardo Bianchi, 180131 Naples, Italy. Tel: +39-081-7064175, Fax: +39-081-7064234; E-mail: [email protected] Received date: Dec 28, 2016, Accepted date: Jan 27, 2017, Published date: Jan 31, 2017 Copyright: © 2017 Giovanni C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Acute thrombus formation is the pathophysiological substrate underlying several clinical conditions, such as acute coronary syndrome (ACS) and stroke. Activation of coagulation cascade is a key step of the thrombotic process: vessel injury results in exposure of the glycoprotein tissue factor (TF) to the flowing blood. Once exposed, TF binds factor VII/VIIa (FVII/FVIIa) and in presence of calcium ions, it forms a tertiary complex able to activate FX to FXa, FIX to FIXa, and FVIIa itself. The final step is thrombin formation at the site of vessel injury with subsequent platelet activation, fibrinogen to fibrin conversion and ultimately thrombus formation. Platelets are the key cells in primary hemostasis.
    [Show full text]
  • Diagnostic Methods in Hematology II
    DiagnosticDiagnostic methodsmethods inin hematologyhematology IIII Jan Zivny Department of Pathophysiology 1. LF UK OutlineOutline Specialized hematology tests • Evaluation of anemia – Anemia basics • Anemia caused by excessive erythrocyte loss • Anemia caused by deficient erythropoiesis • Diagnostic methods used in leukemia/lymphoma ANEMIAANEMIA • WHO criteria: Hb < 125 g/L in adults • US criteria: –M: Hb < 135 g/L –F: Hb < 125 g/L •• AnemiaAnemia isis clinicalclinical signsign CausesCauses ofof anemiaanemia • Insufficient RBC production – deficient erythropoiesis • Excessive RBC loss – Hemolysis (shortened lifespan of erythrocytes) – Acute bleeding (chronic bleeding leads to iron depletion and results in iron loss and deficient erythropoiesis) AnemiaAnemia causedcaused byby deficientdeficient erythropoiesiserythropoiesis Causes of insufficient erythropoiesis? AnemiaAnemia causedcaused byby deficientdeficient erythropoiesiserythropoiesis • Iron metabolism related (microcytic) – Iron deficiency – Chronic diseases • Vitamin B12 or folate deficiency (macrocytic) • Insuficient EPO production and marrow failure (normocytic) – kidney failure – aplastic anemia – myelodysplasia – leukemia DiagnosticDiagnostic aproachesaproaches toto ironiron metabolismmetabolism relatedrelated anemiaanemia IronIron deficiencydeficiency ChronicChronic diseasesdiseases IronIron deficiencydeficiency • microcytic anemia and/or anisocytosis • ↓ blood reticulocytes • hypoproliferative BM • Blood loss in excess of 10 to 20 mL of blood per day (> 5-10 mg of iron) or
    [Show full text]
  • Intrinsic Factor
    ENZYMES INTRINSIC FACTOR EINECS Number 232-711-9 Alternative Names Vitamin B12-binding protein, Factor VII, Intrinsic Factor protein Assay Principle Intrinsic Factor binds specifically to Vitamin B12. The coating of a Vitamin B12-BSA (IF Content) conjugate to the ELISA plate allows for the extent of Intrinsic Factor binding to be investigated. A Mouse monoclonal Anti-Intrinsic Factor antibody is used to identify the concentration of Intrinsic Factor bound to the Vitamin B12. The Antibody bound to the Intrinsic Factor on the plate is identified by use of an Anti Mouse AP conjugate. PNPP substrate is used to develop signals, read at an absorbance of 405nm on a plate reader. What is pernicious anaemia? Key Benefits Intrinsic Factor is primarily used in the diagnosis of pernicious anaemia, a condition caused by a vitamin B12 deficiency. Prevalence in the general + SUPPLY SECURITY population varies from around 3% - 5%, and increases dramatically to Fully manufactured by BBI 5% - 20% among people older than 65 years. Solutions at our Crumlin site, ensuring control over manufacturing processes and supply chain + HIGH PURITY Intrinsic Factor has a purity of >95% ensuring optimal performance in your assay + PROVEN PERFORMANCE Porcine Intrinsic Factor works in a range of immunoassay formats The role of Intrinsic Factor in diagnosis + HIGH QUALITY Intrinsic Factor has a high affinity and specificity to vitamin B12, which Manufactured under a makes it ideal for use in immunoassays. Most commercial assays utilise Quality System compliant a competitive binding technique generating a chemiluminescent signal. with ISO 13485:2016 with Commercial assays can usually detect to a level of ~50 pg/ml vitamin B12.
    [Show full text]
  • In Vitro Modelling of the Mucosa of the Oesophagus and Upper Digestive Tract
    21 Review Article Page 1 of 21 In vitro modelling of the mucosa of the oesophagus and upper digestive tract Kyle Stanforth1, Peter Chater1, Iain Brownlee2, Matthew Wilcox1, Chris Ward1, Jeffrey Pearson1 1NUBI, Newcastle University, Newcastle upon Tyne, UK; 2Applied Sciences (Department), Northumbria University, Newcastle upon Tyne, UK Contributions: (I) Conception and design: All Authors; (II) Administrative support: All Authors; (III) Provision of study materials or patients: All Authors; (IV) Collection and assembly of data: All Authors; (V) Data analysis and interpretation: All Authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Kyle Stanforth. NUBI, Medical School, Framlington Place, Newcastle University, NE2 4HH, Newcastle upon Tyne, UK. Email: [email protected]. Abstract: This review discusses the utility and limitations of model gut systems in accurately modelling the mucosa of the digestive tract from both an anatomical and functional perspective, with a particular focus on the oesophagus and the upper digestive tract, and what this means for effective in vitro modelling of oesophageal pathology. Disorders of the oesophagus include heartburn, dysphagia, eosinophilic oesophagitis, achalasia, oesophageal spasm and gastroesophageal reflux disease. 3D in vitro models of the oesophagus, such as organotypic 3D culture and spheroid culture, have been shown to be effective tools for investigating oesophageal pathology. However, these models are not integrated with modelling of the upper digestive tract—presenting an opportunity for future development. Reflux of upper gastrointestinal contents is a major contributor to oesophageal pathologies like gastroesophageal reflux disease and Barratt’s oesophagus, and in vitro models are essential for understanding their mechanisms and developing solutions.
    [Show full text]
  • Hereditary Intrinsic Factor Deficiency in China Caused by a Novel Mutation
    Ruan et al. BMC Medical Genetics (2020) 21:221 https://doi.org/10.1186/s12881-020-01158-z CASE REPORT Open Access Hereditary intrinsic factor deficiency in China caused by a novel mutation in the intrinsic factor gene—a case report Jing Ruan, Bing Han* , Junling Zhuang, Miao Chen, Fangfei Chen, Yuzhou Huang and Wenzhe Zhou Abstract Background: Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies. Case presentation: A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early terminationmutationinexon5ofGIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed. Conclusions: A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry. Keywords: Megaloblastic anemia, Cobalamin deficiency, Intrinsic factor Background IFD is caused by homozygous or compound heterozy- Vitamin B12 or cobalamin deficiency is characterized by gous mutation in the gene of gastric intrinsic factor on megaloblastic anemia with neurological problems and chromosome 11q12. It presents in early childhood with can be caused by numerous acquired and inherited dis- the lack of gastric intrinsic factor, while the gastric acid eases [1].
    [Show full text]
  • Blood Coagulation Overview and Inherited Hemorrhagic Disorders 2002 Abshire
    Blood Coagulation Overview and Inherited Hemorrhagic Disorders 2002 Abshire 1) Thrombin is one of the key proteins in the coagulation cascade and has both procoagulant and anticoagulant properties. Which one of the following is an important anticoagulation function: a. Activation of factors V and VIII b. Factor XIII activation c. Stimulation of the thrombin activated fibrinolytic inhibitor (TAFI) d. Complex with thrombomodulin (TM). 2) The endothelial cell lining blood vessels possesses several important anticoagulation functions . Which one of the following is one of its' important hemostasis (procoagulant) functions? a. Production of nitric oxide (NO) b. Activation of thrombomodulin (TM) c. Release of plasminogen activator inhibitor (PAI-I) d. Release of TPA e. Interaction of heparin sulfate with anti-thrombin III (AT III) 3) A term well infant is born without complications after a normal pregnancy and initial nursery stay. Upon drawing the metabolic screen, the baby is noted to have prolonged oozing from the heelstick sample. CBC, plt ct, PT, a PTT and fibrinogen were normal. Family history is negative. He returns for the 2 week check and the mother notices that the umbilical cord has been oozing for 4 days. A screening test for factor XIII deficiency is ordered and the baby's clot does not dissolve in 5 M urea. The euglobulin lysis time (ELT) was less than one hour. The most likely diagnosis is: a. Factor XIII heterozygous deficiency b. Homozygous antiplasmin deficiency c. Mild hemophilia B (Factor IX deficiency) d. von Willebrand Disease e. Tissue plasminogen activator (TPA) excess. 4) The newborn's coagulation system is both similar and quite different from a child's.
    [Show full text]
  • General Considerations of Coagulation Proteins
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 8, No. 2 Copyright © 1978, Institute for Clinical Science General Considerations of Coagulation Proteins DAVID GREEN, M.D., Ph.D.* Atherosclerosis Program, Rehabilitation Institute of Chicago, Section of Hematology, Department of Medicine, and Northwestern University Medical School, Chicago, IL 60611. ABSTRACT The coagulation system is part of the continuum of host response to injury and is thus intimately involved with the kinin, complement and fibrinolytic systems. In fact, as these multiple interrelationships have un­ folded, it has become difficult to define components as belonging to just one system. With this limitation in mind, an attempt has been made to present the biochemistry and physiology of those factors which appear to have a dominant role in the coagulation system. Coagulation proteins in general are single chain glycoprotein molecules. The reactions which lead to their activation are usually dependent on the presence of an appropriate surface, which often is a phospholipid micelle. Large molecular weight cofactors are bound to the surface, frequently by calcium, and act to induce a favorable conformational change in the reacting molecules. These mole­ cules are typically serine proteases which remove small peptides from the clotting factors, converting the single chain species to two chain molecules with active site exposed. The sequence of activation is defined by the enzymes and substrates involved and eventuates in fibrin formation. Mul­ tiple alternative pathways and control mechanisms exist throughout the normal sequence to limit coagulation to the area of injury and to prevent interference with the systemic circulation. Introduction RatnofP4 eloquently indicates in an arti­ cle aptly entitled: “A Tangled Web.
    [Show full text]
  • Vitamin B12 Deficiency Cascade: Understanding Nutritional Deficit
    Vitamin B12 Deficiency Cascade: Understanding Nutritional Deficit In the United States and the United Kingdom, vitamin B12 and/or complete blood count (CBC) values suggestive of B12 deficiency is estimated to affect about 6% of people below age deficiency.10 Although often used as the first-line screening test 60 and nearly 20% above age 60.1 for B12 deficiency, serum B12 measurement used in isolation generally has poor sensitivity and specificity for detection of B12 Vitamin B12 is an essential nutrient for the production of deficiency, causing a significant number of patients with vitamin normal red blood cells, DNA synthesis, and normal neurological B12 deficiency to be overlooked.11 function.2 Low B12 status is rarely attributable to dietary insufficiency and is more typically the result of malabsorption LabCorp’s Vitamin B12 Deficiency Cascade (141503) utilizes a related to chronic inflammation of the stomach or the use of sequential selection algorithm to properly identify patients with medications such as proton pump inhibitors and metformin.3,4 vitamin B12 deficiency and to understanding the cause of the One of the most common causes of vitamin B12 deficiency nutritional deficit, such as Pernicious Anemia (see algorithm on is a condition known as Pernicious Anemia (PA), a type of the reverse). In this approach, a second-line assay, Methylmalonic autoimmune-mediated chronic atrophic gastritis.5,6 Patients with Acid (MMA), Serum or Plasma (706961), is performed when the PA lack intrinsic factor proteins, which are essential for
    [Show full text]
  • Gastric Intrinsic Factor the Demonstration, by W
    Gut, 1968, 9, 373-375 Gut: first published as 10.1136/gut.9.4.373 on 1 August 1968. Downloaded from Gastric intrinsic factor The demonstration, by W. B. Castle1 and his collaboraters some 40 years ago of a haemopoietic substance in the gastric secretion absent in pernicious anaemia was the starting point of a chain of observations that has continued to the present time. Intrinsic factor (IF) has now been obtained in a relatively pure state from human gastric juice2 and from hog pyloric mucosa.3It is a mucoprotein with a molecular weight of about 60,000 and contains about 13 % of carbohydrates. Each molecule binds one molecule of vitamin B12, that is, 1 mg of IF binds 25 gg of vitamin B12. In man, as well as in the guinea pig, cat, rabbit, and monkey, IF arises from the gastric parietal cell but surprisingly in the rat and mouse its source is the chief cell.4 Substances that stimulate secretion of hydrochloric acid in man also stimulate that of intrinsic factor. These include histamine and gastrin and their analogues, and insulin. Cholinergic drugs such as carbachol are not effective.5'6 The early and rapid rise in intrinsic factor secretion preceding that of acid has suggested that the stimulus to secretion has washed out preformed IF from the parietal cell. If, however, histamine is infused over a longer period the IF level is main- tained above base line levels indicating a continuous stimulus to increased production.7 The normal stomach produces far more intrinsic factor than is required for vitamin B12 absorption.
    [Show full text]
  • Dazl Regulates Mouse Embryonic Germ Cell Development
    Dazl regulates mouse embryonic germ cell development by Mark E. Gill B.S. Biochemistry and Molecular Biology and Mathematics University at Albany, State University of New York SUBMITTED TO THE DEPARTMENT OF BIOLOGY IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN BIOLOGY AT THE MASSACHUS TS INT E MASSACHUSETTS INSTITUTE OF TECHNOLOGY OF TECHNOLOGY FEB 0 4 2010 FEBRUARY 2010 LIBRARIES @ 2010 Massachusetts Institute of Technology. All rights reserved. ARCHIVES . I Signature of Author: Department of Biology November 2, 2009 Certified by: David C. Page Professor of Biology 'X Jhesis Supervisor Accepted by: Tania Baker Professor of Biology Chair, Committee for Graduate Students Dazl regulates mouse embryonic germ cell development by Mark E. Gill Submitted to the Department of Biology on November 2, 2009 in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biology ABSTRACT In the mouse, germ cells can undergo differentiation to become either oocytes or spermatozoa in response to sex of their gonadal environment. The nature of the germ cell-intrinsic aspects of this signaling have not been well studied. The earliest known sex-specific difference in germ cells is the initiation of meiosis in female, but not male, embryonic germ cells. Experiments were performed showing that germ cells of both sexes transit through a state, the meiosis competent germ cell, that is required for initiation of meiosis. Acquisition of this state requires the function of the germ cell- specific RNA binding protein DAZL. The sufficiency for the absence of meiosis to drive male germ cell differentiation was then tested by examining non-meiotic XX germ cells in the Dazl-deficient ovary.
    [Show full text]
  • Chronic Atrophic Gastritis with Negative Intrinsic Factor and Parietal Cell Antibody Presenting As a Severe Hemolytic Anemia
    Hindawi Case Reports in Hematology Volume 2020, Article ID 8697493, 4 pages https://doi.org/10.1155/2020/8697493 Case Report Chronic Atrophic Gastritis with Negative Intrinsic Factor and Parietal Cell Antibody Presenting as a Severe Hemolytic Anemia G. F. Cittolin-Santos , S. Khalil, J. K. Bakos, and K. Baker Medical University of South Carolina, Department of Internal Medicine, Charleston, SC, USA Correspondence should be addressed to G. F. Cittolin-Santos; [email protected] Received 17 January 2020; Revised 23 April 2020; Accepted 5 May 2020; Published 15 May 2020 Academic Editor: Tom S. J. Gonz lez L pez Copyright © 2020 G. F. Cittolin-Santos et al. ,is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A 28-year-old Caucasian male with Hashimoto’s disease and vitiligo presented with two weeks of dizziness on exertion following pharyngitis which was treated with prednisone 40 mg by mouth once a day for five days. Initial workup revealed anemia, elevated lactate dehydrogenase (LDH), and low haptoglobin. He underwent workup for causes of hemolytic anemia which was remarkable for a peripheral blood smear with hypersegmented neutrophils and low vitamin B12 levels concerning for pernicious anemia. Parietal cell and intrinsic factor antibodies were negative, and he then underwent an esophagogastroduodenoscopy with biopsy. ,e biopsy was negative for Helicobacter pylori, and the immunohistochemical stains were suggestive of chronic atrophic gastritis. He was started on vitamin B12 1,000 mcg intramuscular injections daily. His hemoglobin, LDH, and haptoglobin normalized.
    [Show full text]