DOCSLIB.ORG

Cell Distribution Striking but Temporary Changes in Splenic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cell Distribution Striking but Temporary Changes in Splenic Plasmodium chabaudi chabaudi Infection in Mice Induces Strong B Cell Responses and Striking But Temporary Changes in Splenic Cell Distribution This information is current as of September 25, 2021. Ariel H. Achtman, Mahmood Khan, Ian C. M. MacLennan and Jean Langhorne J Immunol 2003; 171:317-324; ; doi: 10.4049/jimmunol.171.1.317 http://www.jimmunol.org/content/171/1/317 Downloaded from References This article cites 52 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/171/1/317.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 September 25, 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 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 © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Plasmodium chabaudi chabaudi Infection in Mice Induces Strong B Cell Responses and Striking But Temporary Changes in Splenic Cell Distribution1 Ariel H. Achtman,* Mahmood Khan,† Ian C. M. MacLennan,† and Jean Langhorne2* B cells and Abs play a key role in controlling the erythrocytic stage of malaria. However, little is known about the way the humoral response develops during infection. We show that Plasmodium chabaudi chabaudi causes major, but temporary changes in the distribution of leukocytes in the spleen. Despite these changes, an ordered response to infection develops, which includes vigorous extrafollicular growth of plasmablasts and germinal center formation. Early in the response, the lymphocytes in the T zone and follicles become widely spaced, and the edges of these compartments blur. This effect is maximal around the peak of parasitemia. Germinal centers are apparent by day 8, peak at day 20, and persist through day 60. Extrafollicular foci of plasmablasts are visible Downloaded from from day 4 and initiate a very strong plasma cell response. Initially, the plasma cells have a conventional red pulp distribution, but by day 10 they are unconventionally sited in the periarteriolar region of the white pulp. In this region they form clusters occupying part of the area normally filled by T cells. B cells are absent from the marginal zone for at least 30 days after the peak of infection, although flow cytometry shows their continued presence in the spleen throughout infection. Relatively normal splenic architecture is regained by day 60 of infection. These results show that the changes in splenic cell distribution are linked to the presence of parasites and do not seem to interfere with the development of the humoral response. The Journal of Immunology, http://www.jimmunol.org/ 2003, 171: 317–324. cells and Abs are necessary for eliminating the erythro- still be found up to 1 year after infection with P. chabaudi cytic stages of malaria in most experimental models. chabaudi, but their number is significantly reduced compared with B Mice lacking B cells are unable to clear infections with the response 3 mo after infection (14). Together, these data indi- Plasmodium yoelii and Plasmodium chabaudi chabaudi, although cate that the generation or maintenance of memory B cells and in the latter, the early acute phase is controlled to some extent in long-lived plasma cells could be impaired in malaria infection. the absence of Ab (1–3). A role for the humoral immune response One way of examining B cell memory generation is to assess the in protective immunity in human malaria is inferred from the ex- balance between the follicular and extrafollicular B cell response. by guest on September 25, 2021 perimental models and from immuno-epidemiological studies in T-independent Ab responses, which typically induce extrafollicu- which high Ab titers and in some cases restricted Ig isotypes to lar Ab responses, are not associated with functional germinal cen- particular Ags or regions of Ags correlate with immunity. Transfer ters or memory formation (15). Under exceptional conditions, T of immune serum into naive mice or humans can diminish or pre- cell-independent germinal centers can form but do not complete vent infection in the recipient (4, 5). their development (16). By contrast, T-dependent Ags, which pro- Although Ab appears to be important in the blood stages of duce both extrafollicular responses and germinal centers, are as- human malaria, immunity only develops after repeated infections sociated with affinity maturation and sustained Ab responses (17, and is lost without continued exposure to infection. Longitudinal 18). The differentiation between the follicular and extrafollicular studies in malaria-exposed human populations show that Ab levels pathways is performed by studying the four major B cell popula- to several important malarial proteins drop rapidly at the end of the tions of the spleen: naive recirculating B cells, which are mainly malaria transmission season (6–10). This drop in Ab levels is also located in the follicular mantle of the white pulp; germinal center seen after people have left the transmission area (11). These data B cells as the source of memory B cells and long-lived plasma contrast with Ab responses of noninfected mice to nonrenewable cells; plasma cells and their plasmablast precursors; and marginal protein Ags that can be sustained for years (12, 13). In mice, zone B cells, which include both naive and memory cells and give splenic B cells able to respond to infected erythrocytes in vitro can rise to rapid extrafollicular thymus-dependent and thymus-inde- pendent Ab responses (19–21). In the present study, C57BL/6 mice were infected with P. *Division of Parasitology, National Institute for Medical Research, London, United chabaudi chabaudi (AS), and the resulting changes in the splenic Kingdom; and †Medical Research Council Center for Immune Regulation, University architecture as well as the four major B cell populations of the of Birmingham, Edgbaston, Birmingham, United Kingdom spleen were studied by immunohistology and flow cytometry. We Received for publication December 24, 2002. Accepted for publication April 29, 2003. conclude that there are major structural changes in the spleen, but these reflect an ordered response to the parasite rather than a sal- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance vage response to indiscriminate damage. with 18 U.S.C. Section 1734 solely to indicate this fact. 1 This work was supported by the Medical Research Council, U.K., and in part by the Materials and Methods European Union, International Cooperation with Developing Countries CT980363. Animals 2 Address correspondence and reprint requests to Dr. Jean Langhorne, Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 Female C57BL/6 mice bred in the specific pathogen-free unit at the Na- 1AA London, U.K. E-mail address: [email protected] tional Institute for Medical Research (London, U.K.) were used at 6–12 wk Copyright © 2003 by The American Association of Immunologists, Inc. 0022-1767/03/$02.00 318 SPLENIC HUMORAL RESPONSES IN MOUSE MALARIA of age. They were conventionally housed on sterile bedding, food, and hydrated in graded alcohols, cleared with Histoclear (National Diagnostics, water. Hull, U.K.), and mounted in DPX (BDH). Parasites and infection Flow cytometry P. chabaudi chabaudi clone AS was routinely injected from frozen stocks. Single-cell suspensions of spleens were prepared, the erythrocytes lysed 5 Further infections were initiated by i.p. injection of 10 parasitized RBCs with 0.16 M NH4Cl and the cells resuspended in FACS buffer (1% weight obtained from infected mice before the peak of parasitemia, and the to volume ratio BSA, 5 mM EDTA, 0.01% sodium azide in PBS, or FACS infection monitored by Giemsa-stained thin blood films as previously buffer without sodium azide for syndecan-1 staining). Cells (5 ϫ 105) were described (22). incubated with appropriately diluted Abs in the presence of anti-Fc recep- tor Ab to prevent Ab binding via the Fc receptor. Samples were acquired ␥ 3 Immunization with chicken -globulin (CGG) on a FACSCalibur and analyzed with CellQuest software (BD Biosciences, CGG (1 mg/ml; The Jackson Laboratory, Bar Harbor, ME) was mixed 1:1 San Jose´, CA). with 9% potassium-aluminum-sulfate and precipitated with 1 M sodium hydroxide. Mice were immunized i.p. with 25 ␮g alum-precipitated Ag in Cell death ␮ 100- l saline solution. 7-Aminoactinomycin D (7-AAD, Sigma-Aldrich) was used to detect apo- ptotic cells, with the necrotic cell marker propidium iodide used in parallel Abs and other reagents for immunohistology and flow cytometry ϩ to ascertain that the majority of the 7-AAD cells were actually apoptotic. The following Abs and reagents were used in immunohistology: rat anti- Splenocytes were stained as described in the previous section. In the final mouse CD3 (KT3) and rat anti-mouse IgM H chain (LO-MM-9) (Serotec, step, either 7-AAD (1 ␮g/2.5 ϫ 105 cells) or propidium iodide (1 ␮g/2.5 ϫ Oxford, U.K.); rat anti-mouse syndecan-1 (CD138, 09341D; BD Phar- 105 cells; Sigma-Aldrich) was added for 20 or 5 min, respectively. Cells Mingen, Oxford, U.K.); biotinylated peanut agglutinin (PNA; Vector Lab- were then analyzed on the FACSCalibur without further washes.
Load more

Recommended publications
  • Characterization of Murine Macrophages from Bone Marrow
    Wang et al. BMC Immunology 2013, 14:6 http://www.biomedcentral.com/1471-2172/14/6 RESEARCH ARTICLE Open Access Characterization of murine macrophages from bone marrow, spleen and peritoneum Changqi Wang1*†, Xiao Yu1,2†, Qi Cao1, Ya Wang1, Guoping Zheng1, Thian Kui Tan1, Hong Zhao1,3, Ye Zhao1, Yiping Wang1 and David CH Harris1 Abstract Background: Macrophages have heterogeneous phenotypes and complex functions within both innate and adaptive immune responses. To date, most experimental studies have been performed on macrophages derived from bone marrow, spleen and peritoneum. However, differences among macrophages from these particular sources remain unclear. In this study, the features of murine macrophages from bone marrow, spleen and peritoneum were compared. Results: We found that peritoneal macrophages (PMs) appear to be more mature than bone marrow derived macrophages (BMs) and splenic macrophages (SPMs) based on their morphology and surface molecular characteristics. BMs showed the strongest capacity for both proliferation and phagocytosis among the three populations of macrophage. Under resting conditions, SPMs maintained high levels of pro-inflammatory cytokines expression (IL-6, IL-12 and TNF-α), whereas BMs produced high levels of suppressive cytokines (IL-10 and TGF-β). However, SPMs activated with LPS not only maintained higher levels of (IL-6, IL-12 and TNF-α) than BMs or PMs, but also maintained higher levels of IL-10 and TGF-β. Conclusions: Our results show that BMs, SPMs and PMs are distinct populations with different biological functions, providing clues to guide their further experimental or therapeutic use. Keywords: Macrophage, Bone marrow, Spleen, Peritoneum Background macrophage populations could be attributed to their het- Macrophages play an essential role in both innate and erogeneity [4].
    [Show full text]
  • In Situ Observation of Germinal Center Cell Apoptosis During a Secondary Immune Response
    J Clin Exp Hematopathol Vol. 46, No. 2, Nov 2006 Original Article In Situ Observation of Germinal Center Cell Apoptosis During a Secondary Immune Response Hito-aki Saitoh, Kunihiko Maeda, and Mitsunori Yamakawa Germinal centers are highly organized anatomic structures essential for the clonal expansion of germinal center (GC) B- cells and associated somatic hypermutation, isotype switching, selection of the high-affinity B-cells (affinity maturation), and elimination of irrelevant or autoreactive clones. The identification of cellular interactions and regulatory mechanisms controlling apoptosis within GCs is essential for a complete understanding of the cellular and molecular dynamics of the GC reaction. We performed a kinetic analysis of the apoptotic activity occurring within GCs of draining lymph nodes of mice immunized with sheep red blood cells (SRBC) after secondary stimulation. The apoptotic activity of GC cells can be divided into three distinct phases : 1) initial phase (within the first days after immunization), 2) reactive phase (from the 5th day to 15th day after secondary immunization), and 3) late phase (after the 15th day). Apoptosis decreased shortly after secondary immunization followed by an increase to peak after an additional 10 days. Finally, apoptosis of GC cells decreased to basal levels. Administration of apoptosis inhibitors decreased the amount of apoptosis during the reactive phase. These results suggest that the reactive phase may be the critical period in which clonal selection and cellular differentiation
    [Show full text]
  • Thymic Lymphoid Follicles in Autoimmune Diseases
    Keio J. Med. 20: 57-68. 1971 THYMIC LYMPHOID FOLLICLES IN AUTOIMMUNE DISEASES ‡U. HISTOLOGICAL, HISTOCHEMICAL AND ELECTRON MICROSCOPIC STUDIES NORIKAZU TAMAOKI, SONOKO HABU and TORU KAMEYA Department of Pathology, School of Medicine, Keio University, Tokyo (Received for publication May 8, 1971) Thymic lymphoid follicles have been known to occur frequently in patients of myasthenia gravis, Graves' disease and other autoimmune diseases, and occa sionally in the young subjects dying by accident.1,2,3,4,5 Spontaneous as well as experimental lymphoid follicles have also been described in the thymus of rodents 6,7,8,9 The presense of a thymic lymphoid follicle has been interpreted as an indication of an abnormal immunological reaction, since the thymus is not a site of antibody production under normal conditions. 10 The thymus is an epithelial organ separated from mesenchymal tissue by an epithelial barrier on the capsular surface and around the blood vessels.11,12,13,14 On the other hand, lymphoid follicles are usually found in the peripheral lymphoid tissue composed of mesenchymal reticular cells, such as lymph nodes, spleen andd lymphoid tissue associated with gut. The present study was intended to describe histological, histochemical and electron microscopic characteristics of thymic lymphoid follicles in order to con firm whether they were related to epithelial or mesenchymal elements and to clarify their histogenesis in the human thymus. MATERIALS AND METHODS The materials were the same biospied human thymuses as described in the previous report.5 Serial sections in some cases were made from paraffin blocks and stained alternatively with H & E and silver impregnation.
    [Show full text]
  • Toll-Like Receptor 9 Signaling Acts on Multiple Elements of the Germinal Center to Enhance Antibody Responses
    Toll-like receptor 9 signaling acts on multiple elements PNAS PLUS of the germinal center to enhance antibody responses Derek C. Rookhuizena,1 and Anthony L. DeFrancob,2 aDepartment of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, CA 94720; and bDepartment of Microbiology and Immunology, University of California, San Francisco, CA 94143 Edited by David Tarlinton, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia, and accepted by the Editorial Board June 24, 2014 (received for review December 23, 2013) Recent studies have demonstrated important roles of nucleic acid- where they provide survival and selection cues to antigen-pre- sensing Toll-like receptors (TLRs) in promoting protective antibody senting B cells through T-cell receptor (TCR) recognition of responses against several viruses. To dissect how recognition of antigenic peptide–MHC II complexes, costimulatory ligand– nucleic acids by TLRs enhances germinal center (GC) responses, receptor pairs, and cytokine production (8, 15, 16). Recently, + + mice selectively deleted for myeloid differentiation primary- it has become clear that some follicular CXCR5 CD4 T cells are + response protein 88 (MyD88) in B cells or dendritic cells (DCs) were thymically derived FoxP3 regulatory T cells, referred to as fol- immunized with a haptenated protein antigen bound to a TLR9 licular regulatory T (TFR) cells (17–22). Although their function ligand. TLR9 signaling in DCs led to greater numbers of follicular is poorly understood at this point, TFR cells appear to limit the helper T (TFH) cells and GC B cells, and accelerated production of size of the GC response (17–20).
    [Show full text]
  • Germinal Center Formation Motif Signaling in B Cells and Reduced
    Altered Regulation of FcγRII on Aged Follicular Dendritic Cells Correlates with Immunoreceptor Tyrosine-Based Inhibition Motif Signaling in B Cells and Reduced This information is current as Germinal Center Formation of October 3, 2021. Yüksel Aydar, Péter Balogh, John G. Tew and Andras K. Szakal J Immunol 2003; 171:5975-5987; ; doi: 10.4049/jimmunol.171.11.5975 Downloaded from http://www.jimmunol.org/content/171/11/5975 References This article cites 47 articles, 17 of which you can access for free at: http://www.jimmunol.org/content/171/11/5975.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 by guest on October 3, 2021 • Fast Publication! 4 weeks from acceptance to publication *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 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 © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Altered Regulation of Fc␥RII on Aged Follicular Dendritic Cells Correlates with Immunoreceptor Tyrosine-Based Inhibition Motif Signaling in B Cells and Reduced Germinal Center Formation1 Yu¨ksel Aydar,* Pe´ter Balogh,* John G.
    [Show full text]
  • Centers Differentiation Stages in Human Germinal Patterns Reflect
    Cutting Edge: Polycomb Gene Expression Patterns Reflect Distinct B Cell Differentiation Stages in Human Germinal Centers This information is current as of September 27, 2021. Frank M. Raaphorst, Folkert J. van Kemenade, Elly Fieret, Karien M. Hamer, David P. E. Satijn, Arie P. Otte and Chris J. L. M. Meijer J Immunol 2000; 164:1-4; ; doi: 10.4049/jimmunol.164.1.1 Downloaded from http://www.jimmunol.org/content/164/1/1 References This article cites 22 articles, 11 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/164/1/1.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 27, 2021 • Fast Publication! 4 weeks from acceptance to publication *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 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 © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. c Cutting Edge: Polycomb Gene Expression Patterns Reflect Distinct B Cell Differentiation Stages in Human Germinal Centers Frank M. Raaphorst,1* Folkert J. van Kemenade,* Elly Fieret,* Karien M.
    [Show full text]
  • 1 | Page: Immune Cells and Tissues Swailes Cells and Tissues of The
    Cells and Tissues of the Immune System N. Swailes, Ph.D. Department of Anatomy and Cell Biology Rm: B046A ML Tel: 5-7726 E-mail: [email protected] Required reading Mescher AL, Junqueira’s Basic Histology Text and Atlas, 12th Edition, Chapter 20: pp226-2480 Ross MH and Pawlina W, Histology: A text and Atlas, 6th Edition, Chapter 21: pp396-429 Learning objectives 1) Identify the major cells of the immune system and briefly outline their function 2) Describe the general structure of lymphoid tissue 3) Differentiate between primary and secondary immune organs 4) Identify the thymus and discuss the role of its cells in ‘educating’ immature T-cells 5) Identify a lymph node and outline how an immune response is triggered here 6) Identify the spleen and describe the role of red and white pulp in filtering the blood and reacting to blood borne antigens 7) Differentiate between MALT in the oral cavity (tonsils) 8) Know where to find and how to identify examples of BALT and GALT Major Take Home Points A. Lymphoid tissues are composed of different types of lymphocytes and supporting cells within a scaffold of Type III collagen/reticular fibers B. The major primary lymphoid organs are encapsulated organs where immature lymphocytes are born (bone marrow) and become immunocompetent (thymus) C. The major secondary lymphoid organs are encapsulated organs where immunocompetent lymphocytes differentiate into effector cells after exposure to antigen in the blood (spleen) or lymph (nodes) D. Mucosa Associated Lymphoid Tissues (MALT) are un-encapsulated areas of lymphoid tissue within the mucosa of organs that can be identified by their lining epithelium (tonsils, GALT: ileum and appendix, BALT) 1 | Page: Immune Cells and Tissues Swailes A1: Organization of the immune system 5a A.
    [Show full text]
  • B Cell Immunity in Solid Organ Transplantation
    REVIEW published: 10 January 2017 doi: 10.3389/fimmu.2016.00686 B Cell Immunity in Solid Organ Transplantation Gonca E. Karahan, Frans H. J. Claas and Sebastiaan Heidt* Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands The contribution of B cells to alloimmune responses is gradually being understood in more detail. We now know that B cells can perpetuate alloimmune responses in multiple ways: (i) differentiation into antibody-producing plasma cells; (ii) sustaining long-term humoral immune memory; (iii) serving as antigen-presenting cells; (iv) organizing the formation of tertiary lymphoid organs; and (v) secreting pro- as well as anti-inflammatory cytokines. The cross-talk between B cells and T cells in the course of immune responses forms the basis of these diverse functions. In the setting of organ transplantation, focus has gradually shifted from T cells to B cells, with an increased notion that B cells are more than mere precursors of antibody-producing plasma cells. In this review, we discuss the various roles of B cells in the generation of alloimmune responses beyond antibody production, as well as possibilities to specifically interfere with B cell activation. Keywords: HLA, donor-specific antibodies, antigen presentation, cognate T–B interactions, memory B cells, rejection Edited by: Narinder K. Mehra, INTRODUCTION All India Institute of Medical Sciences, India In the setting of organ transplantation, B cells are primarily known for their ability to differentiate Reviewed by: into long-lived plasma cells producing high affinity, class-switched alloantibodies. The detrimental Anat R. Tambur, role of pre-existing donor-reactive antibodies at time of transplantation was already described in Northwestern University, USA the 60s of the previous century in the form of hyperacute rejection (1).
    [Show full text]
  • Extrafollicular Proliferation of B Cells in the Absence of Follicular Hyperplasia
    Histopathology 2005, 47, 90–100. DOI: 10.1111/j.1365-2559.2005.02173.x Extrafollicular proliferation of B cells in the absence of follicular hyperplasia: a distinct reaction pattern in lymph nodes correlated with primary or recall type responses A Brighenti, M Andrulis,1 E Geissinger,1 S Roth,1 HKMu¨ller-Hermelink1 &TRu¨diger1 Istituto di Anatomia Patologica, Universita` degli Studi di Verona, Verona, Italy, and 1Institute of Pathology, University of Wu¨rzburg, Wu¨rzburg, Germany Date of submission 30 April 2004 Accepted for publication 10 March 2005 Brighenti A, Andrulis M, Geissinger E, Roth S, Mu¨ller-Hermelink H K & Ru¨diger T (2005) Histopathology 47, 90–100 Extrafollicular proliferation of B cells in the absence of follicular hyperplasia: a distinct reaction pattern in lymph nodes correlated to primary or recall type responses Aims: Extrafollicular activation of B cells is rarely cases proliferating cells were mainly IgG+CD27+, i.e. observed in human lymph nodes. The aim of this study derived from class-switched postgerminal centre mem- was to extensively analyse the expression of surface ory B cells. Some of these cells expressed CD30. In the molecules and transcription factors in four such cases, other two cases, immunoglobulin-forming cells were comparing them with follicular B cells and medullary non-class-switched IgM+CD27– B cells, representing a cord plasma cells. primary expansion of naive B cells. Methods and results: Various combinations of B-cell- Conclusions: Extrafollicular B-cell activation is the related surface markers and transcription factors were morphological correlate of rapid B-cell responses that studied by triple immunofluorescence.
    [Show full text]
  • Plasma Cells: Finding New Light at the End of B Cell Development Kathryn L
    © 2001 Nature Publishing Group http://immunol.nature.com REVIEW Plasma cells: finding new light at the end of B cell development Kathryn L. Calame Plasma cells are cellular factories devoted entire- Upon plasma cell differentiation, there is a marked increase in ly to the manufacture and export of a single prod- steady-state amounts of Ig heavy and light chain mRNA and, when 2 uct: soluble immunoglobulin (Ig). As the final required for IgM and IgA secretion, J chain mRNA . Whether the increase in Ig mRNA is due to increased transcription, increased mediators of a humoral response, plasma cells mRNA stability or, as seems likely, both mechanisms, remains con- play a critical role in adaptive immunity.Although troversial2. There is also an increase in secreted versus membrane intense effort has been devoted to studying the forms of heavy chain mRNA, as determined by differential use of poly(A) sites that may involve the availability of one component of regulation and requirements for early B cell the polyadenylation machinery, cleavage-stimulation factor Cst-643. development, little information has been avail- To accommodate translation and secretion of the abundant Ig able on plasma cells. However, more recent mRNAs, plasma cells have an increased cytoplasmic to nuclear ratio work—including studies on genetically altered and prominent amounts of rough endoplasmic reticulum and secreto- ry vacuoles. mice and data from microarray analyses—has Numerous B cell–specific surface proteins are down-regulated begun to identify the regulatory cascades that upon plasma cell differentiation, including major histocompatibility initiate and maintain the plasma cell phenotype. complex (MHC) class II, B220, CD19, CD21 and CD22.
    [Show full text]
  • Signals for B Cell Activation in Antibody Response
    Signals for B cell activation in Antibody response YANG ZHANG A thesis is submitted to the University of Birmingham for the degree of Doctor of Philosophy School of immunity & Infection College of Medicine and Dental Science University of Birmingham June 2010 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. Abstract Germinal centres (GCs) are the sites where V-gene hypermutation and B cell selection are taking place. Testing specificity and affinity of GC B cell receptor by interaction with antigen on follicular dendritic cells (FDCs) may be an important selection process to select high affinity B cell clone. As antigen on FDC is present in the form of antigen-antibody immune complex, GC B cells are expected to have to compete with antibody to get access antigen. Initially this antibody will be of low affinity. However, during the course of an immune response, this affinity may increase. We have tested this competitive selection model by following the replacement of antibodies in the GC over the course of an immune response. The speed of this replacement is dependent on affinity.
    [Show full text]
  • The Anatomy of T-Cell Activation and Tolerance Anna Mondino*T, Alexander Khoruts*, and Marc K
    Proc. Natl. Acad. Sci. USA Vol. 93, pp. 2245-2252, March 1996 Review The anatomy of T-cell activation and tolerance Anna Mondino*t, Alexander Khoruts*, and Marc K. Jenkins Department of Microbiology and the Center for Immunology, University of Minnesota Medical School, 420 Delaware Street S.E, Minneapolis, MN 55455 ABSTRACT The mammalian im- In recent years, it has become clear that TCR is specific for a self peptide-class I mune system must specifically recognize a full understanding of immune tolerance MHC complex) T cell that will exit the and eliminate foreign invaders but refrain cannot be achieved with reductionist in thymus and seed the secondary lymphoid from damaging the host. This task is vitro approaches that separate the individ- tissues (3, 4). In contrast, cortical CD4+ accomplished in part by the production of ual lymphocyte from its in vivo environ- CD8+ thymocytes that express TCRs that a large number of T lymphocytes, each ment. The in vivo immune response is a have no avidity for self peptide-MHC bearing a different antigen receptor to well-organized process that involves mul- complexes do not survive and die by an match the enormous variety of antigens tiple interactions of lymphocytes with each apoptotic mechanism. Cortical epithelial present in the microbial world. However, other, with bone-marrow-derived antigen- cells are essential for the process of pos- because antigen receptor diversity is gen- presenting cells (APCs), as well as with itive selection because they display the self erated by a random mechanism, the im- nonlymphoid cells and their products. The peptide-MHC complexes that are recog- mune system must tolerate the function of anatomic features that are designed to op- nized by CD4+ CD8+ thymocytes and also T lymphocytes that by chance express a timize immune tolerance toward innocuous provide essential differentiation factors self-reactive antigen receptor.
    [Show full text]