DOCSLIB.ORG

Original Article CD21 and CD23 Expression Differences in Small B-Cell Lymphomas: Comparative Analysis in Follicular Dendritic Cells and Tumor Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Original Article CD21 and CD23 Expression Differences in Small B-Cell Lymphomas: Comparative Analysis in Follicular Dendritic Cells and Tumor Cells Int J Clin Exp Pathol 2016;9(8):8395-8405 www.ijcep.com /ISSN:1936-2625/IJCEP0029454 Original Article CD21 and CD23 expression differences in small B-cell lymphomas: comparative analysis in follicular dendritic cells and tumor cells Yunfei Shi, Xianghong Li, Yumei Lai, Ling Jia Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China Received March 30, 2016; Accepted June 11, 2016; Epub August 1, 2016; Published August 15, 2016 Abstract: Objective: Different follicular dendritic cells (FDCs) meshwork patterns were observed in small B-cell lym- phomas (SBL) specimens. However, the accurate CD21 and CD23 expression differences in both follicular dendritic cells (FDCs) and tumor cells in SBLs were not sufficiently investigated. Methods: CD21 and CD23 immunostainings were performed on our surgically resected SBL samples to compare their differences in detecting of FDC meshwork immunoarchitectural patterns (FDC patterns), three parameters were introduced for accurate description and com- parison of FDC patterns: including the ratio of FDC meshwork outlined area to total tumor area (ROT), staining inten- sity, and major patterns type (I, expanded follicles with sharp margin; II, contracted follicles with moth-eaten margin; III, ill-defined expanded nodules; IV, absent). The exact expression frequencies of CD21 and CD23 in all SBL groups was also evaluated and compared using double immunohistochemistry (D-IHC). Results: 103 nodal SBL cases, including 32 follicular lymphoma (FL), 28 marginal zone lymphoma (MZL), 23 mantle cell lymphoma (MCL), and 20 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) cases were examined for more accurate data of FDC pattern parameters, including the mean of ROTs, the percentages of cases exhibiting strongly positive staining and the most common distribution patterns. For CD21 and CD23 they were (46.3% and 39.2%), (81.3% and 78.1%) and (type I, accounting for 93.8% and 81.3%) of all cases respectively in the FL group, (21.4% and 16.8%), (56.5% and 82.6%) and (type III, accounting for 47.8% and 52.2%) in the MCL group, (23.7% and 28.6%), (71.4% and 92.8%) and (type II, accounting for 50% and 67.9%) respectively in the MZL group, and (2.2% and 0.3%), (20% and 5%) and (type IV, accounting for 60% and 95% cases) respectively in the CLL/SLL group. No significant differ- ence was seen in CD21 and CD23 labeling of the FDC pattern parameters. Based on the results of D-IHC, CD21 was detected in 28.1%, 60.9%, 60.7% and 55% of the tumor cells from the FL, MCL, MZL and CLL/SLL samples, respectively, and CD23 was detected in 34.4%, 21.7%, 28.6% and 95% of the respective samples. Conclusion: The most common distribution pattern of FDC patterns was identical between these two markers. Both displayed pattern I in FL, III in MCL, II in MZL and IV in CLL/SLL. The D-IHC results showed that both CD21 and CD23 were expressed in partial cases from each SBL subtype. CD21 expression was much less abundant in FL tumor cells, and CD23 expression was much more abundant in CLL/SLL tumor cells. Keywords: B cell lymphoma, follicular dendritic cell, biomarker, comparative study, double immunohistochemical staining Introduction chronic lymphocytic leukemia/small lymphocyt- ic lymphoma (CLL/SLL). There are differences Small B-cell lymphomas (SBL) is not a specific in their clinical presentation, pathobiology, type of B cell non-Hodgkin lymphoma [1, 2], prognosis, as well as specific treatment options, they are often small in cell size, grow in a dif- in accordance with their heterogeneous origin fuse/nodular pattern and all express CD20 [1]. of neoplastic cells, thus, their accurate classifi- In this study, we focused on the four most com- cation is important. mon subtypes of SBL: low-grade follicular lym- phoma (FL, grade 1/2), mantle cell lymphoma Although the classic forms of these entities can (MCL), marginal zone lymphoma (MZL) and be diagnosed by routine histopathologic and CD21 & CD23 expression differences in SBLs immunophenotypic examination, fairly specific evaluate these staining results in differential markers existed in differential diagnosis of SBL diagnosis was further discussed. subtypes, for example, Cyclin D1 in MCL [3, 4], LEF1 in CLL/SLL [5] and germinal center mark- Materials and methods ers in follicular lymphoma [1]. However, accu- Specimen collection rate diagnosis for several instances of SBLs with borderline histopathology/immuno-pheno- Excisional specimens diagnosed as SBL were types might still be difficult. Resent works collected at our department from November revealed reliable microenvironmental findings 2008 to August 2014. The pathological diagno- including follicular dendritic cells (FDC) pat- sis was reviewed by at least two hematopathol- terns could be used as additional markers of ogists according to the WHO 2008 lymphoma differential diagnosis [6-10]. classification. MCL, MZL and FL are follicle-derived lympho- Hematoxylin & eosin staining mas (FDLs) [9], excluding CLL/SLL. Fakan and our previous study [11, 12] also confirmed that Specimens were fixed in 10% neutralized for- there were significant differences in the distri- malin, embedded in paraffin, and cut into 4-μm bution of follicular dendritic cell immunoarchi- thick tissue sections. Morphological character- tectural patterns (FDC patterns) among types istics were observed via hematoxylin & eosin of SBLs on formalin fixed paraffin embedded staining under an Olympus BX43 microscope. (FFPE) tissue, which also demonstrated that alterations in FDC patterns provided supple- Immunohistochemical staining mental assistance in the identification of spe- IHC for CD21 (EP3093, Abcam, Cambridge, UK) cific SBL subtypes. and CD23 (SP23, Thermo Fisher, Rockford, USA) was performed using a BenchMark ULTRA CD3d receptor (CD21) and low affinity IgE automated IHC/ISH staining instrument (Tu- receptor (CD23) were two most frequently mak- cson, VENTANA-Roche, USA) and a ultraVIEW ers used to reveal FDC patterns with immuno- kit (Tucson, VENTANA-Roche, USA). Dilution of histochemistry [3, 13, 14], for FFPE lymphoid CD21 and CD23 in IHC were 1:100. tissues. Troxell’s group [15] reported that CD21 was more sensitive than CD23 for labeling Double immunohistochemical staining FDCs in AITL, and Jin et al. [16] reported that CD23 expression by FDCs was decreased in FL, Double immunohistochemistry (D-IHC) for MCL and AITL relative to healthy controls, but CD21/PAX5 and CD23/PAX5 was performed the alterations in CD21 expression, compari- according to a method described in the litera- son with CD23 expression and CD21 and CD23 ture [18, 19]. Antibodies against CD21 (EP30- expression frequencies on SBL tumor cells 93, Abcam, Cambridge, UK), CD23 (SP23, Ther- were not fully studied, and traditional IHC meth- mo Fisher, Rockford, USA) and Pax5 (ZP007, od would not be sufficient because expression Thermo Fisher, Rockford, USA) were used for of FDC patterns would be mixed with tumor D-IHC, the two antibodies were from mouse cells, for example, CD23 expression was seen (PAX5) and rabbit (CD21&CD23), the dilutions in 94% of the CLL/SLL [17]. of these 3 antibodies were 1:50. The polymer D-IHC chromogen kit (DS201, GBI labs, Bothell, This study would like to present a distinctive USA) was used to detect two different sources new characteristic: it was carried out on SBL of antibodies in the same tissue sections; the samples collected from our department, in an kit contains a goat anti-mouse secondary anti- attempt to accurately identify the differences in body labeled with horseradish peroxidase or a FDC patterns labeled by CD21 and CD23 in all goat anti-rabbit secondary antibody labeled SBL subtypes. Double immunohistochemistry with alkaline phosphatase. For CD21 and of CD21/PAX5 and CD23/PAX5 were also per- CD23, the labeling was Fast Red (red), and DAB formed to determine whether the PAX5-positive was used for the colorimetric detection of Pax5 SBL tumor cells truly express CD21 and/or (brown). All procedures were performed strictly CD23 and the exact frequencies. The value to according to the manufacturers’ instructions. 8396 Int J Clin Exp Pathol 2016;9(8):8395-8405 CD21 & CD23 expression differences in SBLs Briefly, heat-induced epitope retrieval was per- Statistical analysis formed by heating slides in EDTA buffer at pH 8.0 using a stainless pressure cooker for 90 SPSS 17.0 statistical software was used to per- 2 seconds, and all antibodies applied were incu- form χ tests for comparisons of measurement bated overnight in a moist chamber at 4-8°C. data between two antibodies staining and cor- relation analysis and to perform t tests for com- Settings for experimental controls parisons of the mean values of measurement data. Reactive lymph nodes were used as positive controls: In reactive germinal centers (GC), IHC Results for FDC markers showed sharply dense FDC meshwork by both CD21 and CD23, meshed Ultimately, 103 patients were selected. There FDCs of the light zone were much denser than were 32 cases of FL, 23 cases of MCL, 28 those in the dark zone, which was in accor- cases of MZL and 20 cases of CLL/SLL. Given dance with polarization of GC. Signals were that differential pathological diagnosis is usu- located on the cell membrane, in the cytoplasm ally difficult for SBL located in lymph nodes and dendritic processes at high magnification. (here after referred to as “nodal cases”), only The positive D-IHC signals of CD21 and CD23 nodal cases were included to increase the con- on FDCs were red, whereas those of PAX5 were sistency of the results. brown, as detected in mature B lymphocytes. A negative control was also established for IHC or Histological features and tumor growth pattern D-IHC staining (primary antibodies omitted). of the various SBL subtypes Pathological interpretation FL: Most FL (Low-grade) samples exhibited fol- licular distribution pattern (90.6%, 29/32), The following parameters were assessed for while 3 of them had additional diffuse areas accurate comparisons between those two mak- (10.3%, 3/29); other FL cases showed diffuse tu- ers: (1) ratio of FDC meshwork outlined area to mor growth (9.4%, 3/32).
Load more

Recommended publications
  • The Ligands for Human Igg and Their Effector Functions
    antibodies Review The Ligands for Human IgG and Their Effector Functions Steven W. de Taeye 1,2,*, Theo Rispens 1 and Gestur Vidarsson 2 1 Sanquin Research, Dept Immunopathology and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; [email protected] 2 Sanquin Research, Dept Experimental Immunohematology and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands; [email protected] * Correspondence: [email protected] Received: 26 March 2019; Accepted: 18 April 2019; Published: 25 April 2019 Abstract: Activation of the humoral immune system is initiated when antibodies recognize an antigen and trigger effector functions through the interaction with Fc engaging molecules. The most abundant immunoglobulin isotype in serum is Immunoglobulin G (IgG), which is involved in many humoral immune responses, strongly interacting with effector molecules. The IgG subclass, allotype, and glycosylation pattern, among other factors, determine the interaction strength of the IgG-Fc domain with these Fc engaging molecules, and thereby the potential strength of their effector potential. The molecules responsible for the effector phase include the classical IgG-Fc receptors (FcγR), the neonatal Fc-receptor (FcRn), the Tripartite motif-containing protein 21 (TRIM21), the first component of the classical complement cascade (C1), and possibly, the Fc-receptor-like receptors (FcRL4/5). Here we provide an overview of the interactions of IgG with effector molecules and discuss how natural variation on the antibody and effector molecule side shapes the biological activities of antibodies. The increasing knowledge on the Fc-mediated effector functions of antibodies drives the development of better therapeutic antibodies for cancer immunotherapy or treatment of autoimmune diseases.
    [Show full text]
  • Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
    Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only.
    [Show full text]
  • ORIGINAL ARTICLE Flow Cytometric Protein Expression Profiling As a Systematic Approach for Developing Disease-Specific Assays
    Leukemia (2006) 20, 2102–2110 & 2006 Nature Publishing Group All rights reserved 0887-6924/06 $30.00 www.nature.com/leu ORIGINAL ARTICLE Flow cytometric protein expression profiling as a systematic approach for developing disease-specific assays: identification of a chronic lymphocytic leukaemia-specific assay for use in rituximab-containing regimens AC Rawstron, R de Tute, AS Jack and P Hillmen Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals, Leeds, UK Depletion of disease below the levels detected by sensitive sustained remissions only occur in patients achieving an MRD- minimal residual disease (MRD) assays is associated with negative complete response.12 Therefore MRD is increasingly prolonged survival in chronic lymphocytic leukaemia (CLL). being used as an end point for therapeutic trials, and several Flow cytometric MRD assays are now sufficiently sensitive and rapid to guide the duration of therapy in CLL, but generally rely studies are now using the assessment of MRD to define the on assessment of CD20 expression, which cannot be accurately duration of therapy. measured during and after therapeutic approaches containing Approaches using allele-specific oligonucleotide polymerase rituximab. The aim of this study was to use analytical software chain reaction (ASO-PCR) to the immunoglobulin gene of the developed for microarray analysis to provide a systematic B-CLL cell are generally accepted to show the highest sensitivity approach for MRD flow assay development. Samples from CLL for MRD detection. However, more recent four-colour ap- patients (n ¼ 49), normal controls (n ¼ 21) and other B-lympho- proaches show sensitivities nearing that of ASO-PCR6,11,13 with proliferative disorders (n ¼ 12) were assessed with a panel of 66 antibodies.
    [Show full text]
  • New Advances in Leukaemia Immunotherapy by the Use of Chimeric Artificial Antigen Receptors
    Biagi et al. Italian Journal of Pediatrics 2011, 37:46 http://www.ijponline.net/content/37/1/46 ITALIAN JOURNAL OF PEDIATRICS REVIEW Open Access New advances in leukaemia immunotherapy by the use of Chimeric Artificial Antigen Receptors (CARs): state of the art and perspectives for the near future Ettore Biagi*, Virna Marin, Greta Maria Paola Giordano Attianese, Irene Pizzitola, Sarah Tettamanti, Elisabetta Cribioli and Andrea Biondi Abstract Leukaemia immunotherapy represents a fascinating and promising field of translational research, particularly as an integrative approach of bone marrow transplantation. Adoptive immunotherapy by the use of donor-derived expanded leukaemia-specific T cells has showed some kind of clinical response, but the major advance is nowadays represented by gene manipulation of donor immune cells, so that they acquire strict specificity towards the tumour target and potent lytic activity, followed by significant proliferation, increased survival and possibly anti- tumour memory state. This is achieved by gene insertion of Chimeric T-cell Antigen Receptors (CARs), which are artificial molecules containing antibody-derived fragments (to bind the specific target), joined with potent signalling T-Cell Receptor (TCR)-derived domains that activate the manipulated cells. This review will discuss the main application of this approach particularly focusing on the paediatric setting, raising advantages and disadvantages and discussing relevant perspectives of use in the nearest future. Keywords: Leukaemia immunotherapy,
    [Show full text]
  • Primary Splenic and Nodal Marginal Zone Lymphoma
    J. Clin. Exp. Hematopathol Vol. 45, No. 1, Aug 2005 Review Article Primary Splenic and Nodal Marginal Zone Lymphoma: Jacques Diebold, Agne`s Le Tourneau, Eva Comperat, Thierry Molina and Jose´ e Audouin Primary splenic and nodal marginal zone (MZ) lymphomas are rare small B cell lymphomas presenting with similar histopathologic features. The neoplastic cell population mostly consists of monocytoid B cells organized in a MZ pattern, associated with centrocytoid cells colonizing follicles. About 50% of cases have a monotypic plasma cell component. The different histopathologic patterns and differential diagnosis are discussed here. Both diseases share a similar immunophenotype, with the expression of B-cell associated antigens and restriction of immunoglobulin light chain. The only difference is the more frequent expression of IgD in splenic than in nodal lymphomas. The most recent findings in genetics and molecular biology are presented and discussed. The main clinical and biological symptoms are described and the similarity of some cases with Waldenstro¨ms macroglobulinemia is stressed. Both lymphomas present with the same type of bone marrow involvement with a high frequency of intravascular infiltrates, which can be associated with interstitial and nodular infiltrates. Transformation into diffuse large B cell lymphoma occurs in about 10 to 15% of the cases. The outcome in many splenic MZ lymphomas is characterized by a lengthy survival after splenectomy (9 to 13 years or longer), despite the absence of a consensus on the optimal treatment. Nodal MZ lymphoma has a more aggressive evolution and seems to only be curable at an early stage. Further studies are needed of both lymphomas to improve treatment and prognosis.
    [Show full text]
  • Slan Monocytes and Macrophages Mediate CD20-Dependent B-Cell
    Published OnlineFirst May 10, 2018; DOI: 10.1158/0008-5472.CAN-17-2344 Cancer Tumor Biology and Immunology Research slanþ Monocytes and Macrophages Mediate CD20-Dependent B-cell Lymphoma Elimination via ADCC and ADCP William Vermi1,2, Alessandra Micheletti3, Giulia Finotti3, Cristina Tecchio4, Federica Calzetti3, Sara Costa3, Mattia Bugatti1, Stefano Calza5, Claudio Agostinelli6, Stefano Pileri7, Piera Balzarini1, Alessandra Tucci8, Giuseppe Rossi8, Lara Furlani4, Giuseppe Todeschini4, Alberto Zamo9, Fabio Facchetti1, Luisa Lorenzi1, Silvia Lonardi1, and Marco A. Cassatella3 Abstract þ Terminal tissue differentiation and function of slan monocytes in cancer þ + + is largely unexplored. Our recent studies demonstrated that slan mono- slan monocyte slan macrophage cytes differentiate into a distinct subset of dendritic cells (DC) in human CD16A þ tonsils and that slan cells colonize metastatic carcinoma-draining lymph CD32 nodes. Herein, we report by retrospective analysis of multi-institutional þ CD16A CD64 cohorts that slan cells infiltrate various types of non-Hodgkin lymphomas = RTX (NHL), particularly the diffuse large B-cell lymphoma (DLBCL) group, CD20 þ CD20 including the most aggressive, nodal and extranodal, forms. Nodal slan cells displayed features of either immature DC or macrophages, in the latter case ingesting tumor cells and apoptotic bodies. We also found in patients þ þ with DLBCL that peripheral blood slan monocytes, but not CD14 monocytes, increased in number and displayed highly efficient rituxi- Lymphoma cell Lymphoma cell mab-mediated antibody-dependent cellular cytotoxicity, almost equivalent + RTX þ to that exerted by NK cells. Notably, slan monocytes cultured in condi- tioned medium from nodal DLBCL (DCM) acquired a macrophage-like + RTX phenotype, retained CD16 expression, and became very efficient in ritux- imab-mediated antibody-dependent cellular phagocytosis (ADCP).
    [Show full text]
  • CD32+ and PD-1+ Lymph Node CD4 T Cells Support Persistent HIV-1
    bioRxiv preprint doi: https://doi.org/10.1101/329938; this version posted May 24, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 CD32+ and PD-1+ Lymph Node CD4 T Cells Support Persistent HIV-1 2 Transcription in Treated Aviremic Individuals 3 Alessandra Notoa, Francesco A. Procopioa, Riddhima Bangaa, Madeleine Suffiottia, Jean-Marc 4 Corpatauxb, Matthias Cavassinic, Craig Fenwicka, Raphael Gottardod, Matthieu Perreaua, 5 Giuseppe Pantaleoa,e# 6 7 aService of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, 8 Lausanne, Switzerland 9 bService of Vascular Surgery, Lausanne University Hospital, University of Lausanne, Lausanne, 10 Switzerland 11 cService of Infectious Diseases, Lausanne University Hospital, University of Lausanne, 12 Lausanne, Switzerland 13 dVaccine and Infectious Disease Divisions, Fred Hutchinson Cancer Research Center, Seattle, 14 Washington, USA 15 eSwiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, 16 Lausanne, Switzerland 17 Running Head: Role of CD32 and PD-1 in Defining the HIV Reservoir 18 #Address correspondence to Giuseppe Pantaleo, [email protected] 19 Word count for the abstract: 318 Word count for the text: 4130 20 1 bioRxiv preprint doi: https://doi.org/10.1101/329938; this version posted May 24, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 21 ABSTRACT 22 A recent study conducted in blood has proposed CD32 as the marker identifying the ‘elusive’ HIV 23 reservoir. We have investigated the distribution of CD32+ CD4 T cells in blood and lymph nodes 24 (LNs) of healthy HIV-1 uninfected, viremic untreated and long-term treated HIV-1 infected 25 individuals and their relationship with PD-1+ CD4 T cells.
    [Show full text]
  • Cells, Tissues and Organs of the Immune System
    Immune Cells and Organs Bonnie Hylander, Ph.D. Aug 29, 2014 Dept of Immunology [email protected] Immune system Purpose/function? • First line of defense= epithelial integrity= skin, mucosal surfaces • Defense against pathogens – Inside cells= kill the infected cell (Viruses) – Systemic= kill- Bacteria, Fungi, Parasites • Two phases of response – Handle the acute infection, keep it from spreading – Prevent future infections We didn’t know…. • What triggers innate immunity- • What mediates communication between innate and adaptive immunity- Bruce A. Beutler Jules A. Hoffmann Ralph M. Steinman Jules A. Hoffmann Bruce A. Beutler Ralph M. Steinman 1996 (fruit flies) 1998 (mice) 1973 Discovered receptor proteins that can Discovered dendritic recognize bacteria and other microorganisms cells “the conductors of as they enter the body, and activate the first the immune system”. line of defense in the immune system, known DC’s activate T-cells as innate immunity. The Immune System “Although the lymphoid system consists of various separate tissues and organs, it functions as a single entity. This is mainly because its principal cellular constituents, lymphocytes, are intrinsically mobile and continuously recirculate in large number between the blood and the lymph by way of the secondary lymphoid tissues… where antigens and antigen-presenting cells are selectively localized.” -Masayuki, Nat Rev Immuno. May 2004 Not all who wander are lost….. Tolkien Lord of the Rings …..some are searching Overview of the Immune System Immune System • Cells – Innate response- several cell types – Adaptive (specific) response- lymphocytes • Organs – Primary where lymphocytes develop/mature – Secondary where mature lymphocytes and antigen presenting cells interact to initiate a specific immune response • Circulatory system- blood • Lymphatic system- lymph Cells= Leukocytes= white blood cells Plasma- with anticoagulant Granulocytes Serum- after coagulation 1.
    [Show full text]
  • Immunohistochemical Expression of CD23 and CD40 May Identify Prognostically Favorable Subgroups of Diffuse Large B-Cell Lymphoma: a Nordic Lymphoma Group Study1
    722 Vol. 9, 722–728, February 2003 Clinical Cancer Research Immunohistochemical Expression of CD23 and CD40 May Identify Prognostically Favorable Subgroups of Diffuse Large B-cell Lymphoma: A Nordic Lymphoma Group Study1 Johan Linderoth,2 Mats Jerkeman, to a germinal center origin or attributable to increased Eva Cavallin-Ståhl, Stein Kvaløy, and apoptosis via induction of bax and/or enhanced T-cell inter- Emina Torlakovic action, resulting in improved autologous tumor response. Confirmatory studies are necessary. Department of Oncology, Lund University Hospital, 221 85 Lund, Sweden [J. L., M. J., E. C-S.]; Department of Oncology, the Norwegian Radium Hospital, Oslo, Norway [S. K.]; and Department INTRODUCTION of Pathology, The Norwegian Radium Hospital, Oslo, Norway [E. T.] DLBCL3 is the most frequent lymphoma subtype and en- compasses the majority, ϳ60–70%, of the aggressive lympho- mas. Biologically and clinically, it shows considerable hetero- ABSTRACT geneity. Eventually, 30–40% of the patients with advanced Purpose: In search for subgroups of diffuse large B-cell stage DLBCL who are treated with current therapies will be lymphoma (DLBCL) with different histogenetic origin and long-time survivors, whereas the rest will succumb to the dis- prognosis, as has been described by gene expression profil- ease. There is an obvious need for prognostic information to ing, we examined tumor specimens from 125 patients with design a more risk-adapted primary therapy. The IPI is one DLBCL, uniformly treated by either cyclophosphamide- available, validated tool, based on clinical features (age, stage, Adriamycin-vincristine-prednisone or methotrexate, doxo- level of lactate dehydrogenase, performance status, and number rubicin, cyclophosphamide, vincristine, prednisone, and of extranodal sites; Ref.
    [Show full text]
  • Genetic Modification of Human T Lymphocytes for the Treatment of Hematologic Malignancies
    REVIEW ARTICLE Genetic modification of human T lymphocytes for the treatment of hematologic malignancies Valentina Hoyos, 1,2 Barbara Savoldo, 1,2 and Gianpietro Dotti 1,2,4 1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston; 2Department of Medicine, Baylor College of Medicine, Houston; 3Department of Pediatrics, Texas Children’s Hospital, Houston; and 4Department of Immunology, Baylor College of Medicine, Houston, USA ABSTRACT Modern chemotherapy regimens and supportive care have post-transplant lymphomas and Hodgkin’s lymphomas. produced remarkable improvements in the overall survival of Because of this compelling clinical evidence and the con - patients with hematologic malignancies. However, the comitant development of methodologies for robust gene development of targeted small molecules, monoclonal anti - transfer to human T lymphocytes, the field has rapidly bodies, and biological therapies that demonstrate greater evolved, offering new opportunities to extend T-cell based efficacy and lower toxicity remains highly desirable in hema - therapies. This review summarizes the most recent biologi - tology, and oncology in general. In the context of biological cal and clinical developments using genetically manipulated therapies, T-lymphocyte based treatments have enormous T cells for the treatment of hematologic malignancies. potential. Donor lymphocyte infusion in patients relapsed after allogeneic hematopoietic stem cell transplant pioneered Key words: immunotherapy, cytotoxic T lymphocytes, gene the concept that T lymphocytes can effectively control transfer, chimeric antigen receptor, suicide gene. tumor growth, and this was then followed by the develop - ment of cell culture strategies to generate T lymphocytes Citation: Hoyos V, Savoldo B, and Dotti G. Genetic modification of with selective activity against tumor cells.
    [Show full text]
  • Delayed Onset of Autoreactive Antibody Production and M2
    www.nature.com/scientificreports OPEN Delayed onset of autoreactive antibody production and M2- skewed macrophages contribute to Received: 6 October 2017 Accepted: 9 January 2018 improved survival of TACI defcient Published: xx xx xxxx MRL-Fas/Lpr mouse Lunhua Liu1, Windy Rose Allman1, Adam Steven Coleman1, Kazuyo Takeda2, Tsai-Lien Lin3 & Mustafa Akkoyunlu1 Anti-B cell activating factor belonging to TNF-family (BAFF) antibody therapy is indicated for the treatment of patients with active systemic lupus erythematosus (SLE). We hypothesized that the BAFF receptor, transmembrane activator and calcium-modulator and cyclophilin interactor (TACI) may be responsible for the generation of antibody secreting plasma cells in SLE. To test this hypothesis, we generated TACI defcient MRL-Fas/Lpr (LPR-TACI−/−) mouse. TACI defciency resulted in improved survival of MRL-Fas/Lpr mice and delayed production of anti-dsDNA and anti-SAM/RNP antibodies. There was also a delay in the onset of proteinuria and the accumulation of IgG and infammatory macrophages (Mφs) in the glomeruli of young LPR-TACI−/− mice compared to wild-type mice. Underscoring the role of TACI in infuencing Mφ phenotype, the transfer of Mφs from 12-week-old LPR- TACI−/− mice to age-matched sick wild-type animals led to a decrease in proteinuria and improvement in kidney pathology. The fact that, in LPR-TACI−/− mouse a more pronounced delay was in IgM and IgG3 autoreactive antibody isotypes and the kinetics of follicular helper T (Tf) cell-development was comparable between the littermates suggest a role for TACI in T cell-independent autoantibody production in MRL-Fas/Lpr mouse prior to the onset of T cell-dependent antibody production.
    [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]