DOCSLIB.ORG

Cell-Expressed CD154 in Germinal Centers Expression, Regulation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cell-Expressed CD154 in Germinal Centers Expression, Regulation Expression, Regulation, and Function of B Cell-Expressed CD154 in Germinal Centers Amrie C. Grammer, Richard D. McFarland, Jonathan Heaney, Bonnie F. Darnell and Peter E. Lipsky This information is current as of September 25, 2021. J Immunol 1999; 163:4150-4159; ; http://www.jimmunol.org/content/163/8/4150 Downloaded from References This article cites 74 articles, 33 of which you can access for free at: http://www.jimmunol.org/content/163/8/4150.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • 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 *average by guest on September 25, 2021 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 © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Expression, Regulation, and Function of B Cell-Expressed CD154 in Germinal Centers1 Amrie C. Grammer,* Richard D. McFarland,† Jonathan Heaney,* Bonnie F. Darnell,† and Peter E. Lipsky2* Activated B cells and T cells express CD154/CD40 ligand in vitro. The in vivo expression and function of B cell CD154 remain unclear and therefore were examined. Tonsillar B and T cells expressed CD154 at a similar density both in situ and immediately ex vivo, whereas a significantly higher percentage of the former expressed CD154. CD154-expressing B cells were most frequent in the CD38positiveIgD1 pre-germinal center (GC)/GC founder, CD38positive GC and CD382IgD2 memory populations, and were also found in the CD382IgD1 naive and CD38brightIgD1 plasmablast subsets, but not in the CD38brightIgD2 plasma cell subset. B cell expression of CD154 was induced by engaging surface Ig or CD40 by signals that predominantly involved activation of AP-1/NF-AT and NF-kB, respectively. The functional importance of CD154-mediated homotypic B cell interactions in vivo was Downloaded from indicated by the finding that mAb to CD154 inhibited differentiation of CD38positiveIgD2 GC B cells to CD382IgD2 memory cells. In addition, mAb to CD154 inhibited proliferation induced by engaging sIg or CD40, indicating the role of up-regulation of this molecule in facilitating B cell responsiveness. Of note, CD154 itself not only functioned as a ligand but also as a direct signaling molecule as anti-CD154-conjugated Sepharose beads costimulated B cell responses induced by engaging surface Ig. These results indicate that CD154 is expressed by human B cells in vivo and plays an important role in mediating B cell responses. The Journal of Immunology, 1999, 163: 4150–4159. http://www.jimmunol.org/ cells express CD154/CD40 ligand following activation in cient in CD40 (12–14) or its ligand (CD154) (14–16) do not form vitro by ionomycin and phorbol ester (1–3) as well as by functional GCs following immunization with T-dependent (TD) B the polyclonal B cell activators Staphyloccus aureus Ag. Additionally, humans with X-linked hyper-IgM syndrome Cowan I (1, 2) or LPS (4, 5). The finding that CD154 expressed by (HIgMXL) syndrome, who cannot express a functional CD154 (re- activated B cells mediates homotypic CD154-CD40 interactions viewed in Refs. 17 and 18) do not form functional GCs in response resulting in aggregation, clonal expansion, and differentiation into to TD Ag (19, 20). Ig-secreting cells (1, 2, 4, 5) suggests that up-regulation of this The GC is one of the structures in which maturation of the by guest on September 25, 2021 molecule might play an essential role in propagating humoral re- humoral response to Ag occurs, fostering somatic hypermutation, sponses in vivo. Further support for this possibility is the finding selection, and isotype switching of activated B cells (reviewed in that circulating B cells from patients with autoimmune diseases, Refs. 21–23). Although CD154-CD40 interactions are essential for such as systemic lupus erythematosus, characterized by polyclonal initiation and propagation of the GC reaction, there are stages of B cell activation express CD154 (5–7). Moreover, certain B cell the GC reaction that appear to proceed in the absence of CD1541 lymphomas express CD154 in a functional manner (8–11). These T cells. CD1541 T cells are absent from the dark zone (DZ), where considerations prompted an examination of whether CD154 is ex- rapid B cell proliferation and somatic hypermutation occur, and are pressed physiologically in vivo at sites of B cell activation in sec- found infrequently if at all in the basal light zone (LZ) of the GC ondary lymphoid tissue as well as a delineation of the regulation of (24–28), where high avidity Ag-binding B cells are rescued from B cell CD154 expression and its functional activity. apoptosis (29, 30). Despite the paucity of CD154-expressing T Signaling through CD40 is important in the formation and per- cells, an established GC rapidly disassembles when CD154-CD40 petuation of the germinal center (GC)3 reaction since mice defi- interactions are blocked (31). One possible explanation for this finding is that cells other than T cells express CD154 in the DZ and LZ of GCs in secondary lymphoid tissues. Activated CD154-ex- *Harold C. Simmons Arthritis Research Center and Departments of Internal Medicine pressing B cells are prime candidates to provide the essential † and Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235 CD40-mediated signals in these regions. Received for publication February 24, 1999. Accepted for publication July 29, 1999. To test this hypothesis requires an examination of CD154 ex- The costs of publication of this article were defrayed in part by the payment of page pression by B cells in secondary lymphoid organs. In humans, charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. tonsils have been employed extensively to understand GC behav- 1 This research was supported by National Institutes of Health (NIH) Grant AI-31229. ior, despite their chronic inflammatory and often infected character A.C.G. was supported in part by NIH Postdoctoral Training Grant AR-18550. (reviewed in Ref. 32). Therefore, the current experiments were 2 Address correspondence and reprint requests to Dr. Peter E. Lipsky, Harold C. undertaken to determine whether CD154 is expressed in situ by Simmons Arthritis Research Center, University of Texas Southwestern Medical Cen- tonsillar B cells, to examine the nature of signals that regulate B ter, 5323 Harry Hines Boulevard, Dallas, TX 75235-8884. E-mail address: [email protected] cell CD154 expression, and to investigate the functional activity of 3 Abbreviations used in this paper: GC, germinal center; MFI, mean fluorescence CD154 expressed by human B cells. The data clearly indicate that intensity; TD, T-dependent; DZ, dark zone; LZ, light zone; sIg, surface Ig; hIg, human CD154 is expressed by tonsillar B cells, is up-regulated by en- Ig; Cy, cyclosporine; MNC, mononuclear cell; MKK1, mitogen-activated protein ki- nase kinase 1; LAC, lactacystein; HIgMXL syndrome, X-linked hyper-IgM syn- gagement of surface Ig (sIg) or CD40 itself, and is likely to be of drome. great importance in propagating GC reactions. Copyright © 1999 by The American Association of Immunologists 0022-1767/99/$02.00 The Journal of Immunology 4151 Materials and Methods Ridgefield, CT) or biotinylated h2431 followed by either streptavidin Cells conjugated to PE (Becton Dickinson), 613, or 670 (Life Technologies). Alternatively, CD154 expression was analyzed with 8976-PE (Becton Tonsils were minced and digested in RPMI medium (Life Technologies, Dickinson) or with 2443 (kind gift of Dr. Randolph J. Noelle) or uncon- Grand Island, NY) containing 210 U/ml collagenase type I (Worthington jugated 8976, followed by biotinylated rat anti-mouse Ig and streptavidin- Biochemical, Lakewood, NJ) and 90 KU/ml DNase (Sigma, St. Louis, PE. In some cases, B cells were acid washed as described (1) to remove MO) for 30 min at 37°C. Following filtration through a wire mesh, the cells bound CD40 before staining with anti-CD154 mAb. Subsets of tonsillar B were washed twice in 20% NHS-RPMI and once with 10% NHS-RPMI. cells were delineated with Ab specific for CD19 (PerCP, APC, Becton Mononuclear cells (MNC) were obtained by centrifugation of heparinized Dickinson; biotinylated, Coulter), IgD (FITC, Caltag; PE, Southern Bio- venous blood or digested tonsil tissue over diatrizoate/Ficoll gradients technology, Birmingham, AL), CD38 (HB7, APC or PE, Becton Dickin- (Sigma). Blood was obtained from healthy adult volunteers or an HIgMXL son; HIT2, FITC, Caltag), CD23 (biotinylated, The Binding Site, San Di- patient previously demonstrated to lack functional CD154 expression. The ego, CA; FITC, Becton Dickinson), TdT (FITC, Supertech, Rockville, mutations in CD154 of this HIgMXL patient have been reported (Refs. 1, MD), Ki67 (Biogenics, Ramon, CA) followed by anti-mouse IgG1 (FITC, 33; EMBL accession number X96710). In some cases, MNCs were de- The Binding Site), CD44 (A3D8, biotinylated, ATCC), and CD77 (Biode- 9 pleted of NK cells and monocytes and separated into T cell-enriched and sign, Kennebunk, ME) followed by goat F(ab )2 anti-rat IgM FITC (Jack- B cell-enriched populations as described (1). The B cell population was son ImmunoResearch). Isotype-matched mAb were used as controls. Anal- further purified by positive selection on a Ceprate streptavidin column ysis was performed using CellQuest and Paint-a-Gate Software (Becton (CellPro, Bothell, WA) following staining of cells with biotinylated anti- Dickinson).
Load more

Recommended publications
  • Increased Expression of CD154 and FAS in SLE Patients’ Lymphocytes Maria Elena Manea, Ruediger B
    Increased expression of CD154 and FAS in SLE patients’ lymphocytes Maria Elena Manea, Ruediger B. Mueller, Doru Dejica, Ahmed Sheriff, Georg Schett, Martin Herrmann, Peter Kern To cite this version: Maria Elena Manea, Ruediger B. Mueller, Doru Dejica, Ahmed Sheriff, Georg Schett, et al.. Increased expression of CD154 and FAS in SLE patients’ lymphocytes. Rheumatology International, Springer Verlag, 2009, 30 (2), pp.181-185. 10.1007/s00296-009-0933-4. hal-00568285 HAL Id: hal-00568285 https://hal.archives-ouvertes.fr/hal-00568285 Submitted on 23 Feb 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Increased expression of CD154 and FAS in SLE patients’ lymphocytes Maria Elena Manea1‡, MD, Ruediger B. Mueller2,3‡, MD, Doru Dejica1, PhD, Ahmed Sheriff2, PhD, Georg Schett2, MD, Martin Herrmann2, PhD, Peter Kern4, MD 1 Department of Immunopathology. “Iuliu Hatieganu" University of Medicine and Pharmacy, Str Croitorilor no 19-21, 3400 Cluj-Napoca, Romania. 2 Department for Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nürnberg, Germany 3 Departement of Rheumatologie, Kantonsspital St. Gallen, Switzerland 4 Franz von Prümmer Klinik, Bahnhofstraße 16, 97769 Bad Brückenau, Germany ‡ both authors equally contributed to the work Address correspondence and reprint requests to: Ruediger B.
    [Show full text]
  • B Cell Checkpoints in Autoimmune Rheumatic Diseases
    REVIEWS B cell checkpoints in autoimmune rheumatic diseases Samuel J. S. Rubin1,2,3, Michelle S. Bloom1,2,3 and William H. Robinson1,2,3* Abstract | B cells have important functions in the pathogenesis of autoimmune diseases, including autoimmune rheumatic diseases. In addition to producing autoantibodies, B cells contribute to autoimmunity by serving as professional antigen- presenting cells (APCs), producing cytokines, and through additional mechanisms. B cell activation and effector functions are regulated by immune checkpoints, including both activating and inhibitory checkpoint receptors that contribute to the regulation of B cell tolerance, activation, antigen presentation, T cell help, class switching, antibody production and cytokine production. The various activating checkpoint receptors include B cell activating receptors that engage with cognate receptors on T cells or other cells, as well as Toll-like receptors that can provide dual stimulation to B cells via co- engagement with the B cell receptor. Furthermore, various inhibitory checkpoint receptors, including B cell inhibitory receptors, have important functions in regulating B cell development, activation and effector functions. Therapeutically targeting B cell checkpoints represents a promising strategy for the treatment of a variety of autoimmune rheumatic diseases. Antibody- dependent B cells are multifunctional lymphocytes that contribute that serve as precursors to and thereby give rise to acti- cell- mediated cytotoxicity to the pathogenesis of autoimmune diseases
    [Show full text]
  • Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency
    Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD, David A. Khan, MD, Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD, David I. Bernstein, MD, Joann Blessing-Moore, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Chief Editor: Francisco A. Bonilla, MD, PhD Co-Editor: David A. Khan, MD Members of the Joint Task Force on Practice Parameters: David I. Bernstein, MD, Joann Blessing-Moore, MD, David Khan, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Primary Immunodeficiency Workgroup: Chairman: Francisco A. Bonilla, MD, PhD Members: Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD GlaxoSmithKline, Merck, and Aerocrine; has received payment for lectures from Genentech/ These parameters were developed by the Joint Task Force on Practice Parameters, representing Novartis, GlaxoSmithKline, and Merck; and has received research support from Genentech/ the American Academy of Allergy, Asthma & Immunology; the American College of Novartis and Merck.
    [Show full text]
  • Single-Cell Analysis of Crohn's Disease Lesions Identifies
    bioRxiv preprint doi: https://doi.org/10.1101/503102; this version posted December 20, 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. Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy JC Martin1,2,3, G Boschetti1,2,3, C Chang1,2,3, R Ungaro4, M Giri5, LS Chuang5, S Nayar5, A Greenstein6, M. Dubinsky7, L Walker1,2,5,8, A Leader1,2,3, JS Fine9, CE Whitehurst9, L Mbow9, S Kugathasan10, L.A. Denson11, J.Hyams12, JR Friedman13, P Desai13, HM Ko14, I Laface1,2,8, Guray Akturk1,2,8, EE Schadt15,16, S Gnjatic1,2,8, A Rahman1,2,5,8, , M Merad1,2,3,8,17,18*, JH Cho5,17,*, E Kenigsberg1,15,16,17* 1 Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 2 Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 3 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 4 The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA. 5 Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. 6 Department of Colorectal Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA 7 Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
    [Show full text]
  • Human CD154 (CD40 Ligand) Recombinant Protein Catalog Number: 14-8502 Also Known As:CD40L, CD40-L RUO: for Research Use Only
    Human CD154 (CD40 Ligand) Recombinant Protein Catalog Number: 14-8502 Also Known As:CD40L, CD40-L RUO: For Research Use Only Product Information Contents: Human CD154 (CD40 Ligand) Recombinant Protein Formulation: Sterile liquid: phosphate buffered saline, pH 7.2, Catalog Number: 14-8502 1.0% BSA. 0.22 µm filtered. Handling Conditions: For best recovery, quick-spin vial prior to Temperature Limitation: Store at less than or equal to -70°C. opening. Use in a sterile environment Batch Code: Refer to Vial Source: E. coli Use By: Refer to Vial Purity: Greater than 98%, as determined by SDS-PAGE Endotoxin Level: Less than 0.01 ng/ug cytokine as determined by the LAL assay. Bioactivity: The ED50 measured in a T-47D cell line proliferation assay is typically 40 ng/ml, corresponding to a specific activity of approximately 2.5 x104 Units/mg. Description CD40 ligand, (CD40L, also known as CD154, TRAP or gp39) is a membrane glycoprotein expressed on activated CD4+ T-cells, NK cells, mast cells, basophils and eosinophils. The CD40-CD40L interaction stimulates B cell immune response which includes cell surface antigen expression, cell cycle activation, Ig isotype switching, Ig secretion and memory generation. The CD40-CD40L interaction also plays important roles in monocyte and dendritic cell activation, T-cell co-stimulation and cytokine production. It has been reported that the CD40-CD40L interaction is involved in the pathogenesis of amyloid pathology in Alzheimer disease. Recombinant Human CD40L produced in E.Coli is a non-glycosylated, polypeptide containing 149 amino acids and having a molecular mass of 16 kDa.
    [Show full text]
  • CD154-Independent Rejection Critical Role of OX40 in CD28
    Critical Role of OX40 in CD28 and CD154-Independent Rejection Gülçin Demirci, Farhana Amanullah, Reshma Kewalaramani, Hideo Yagita, Terry B. Strom, Mohamed H. This information is current as Sayegh and Xian Chang Li of October 1, 2021. J Immunol 2004; 172:1691-1698; ; doi: 10.4049/jimmunol.172.3.1691 http://www.jimmunol.org/content/172/3/1691 Downloaded from References This article cites 42 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/172/3/1691.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 *average by guest on October 1, 2021 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 © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Critical Role of OX40 in CD28 and CD154-Independent Rejection1 Gu¨lc¸in Demirci,* Farhana Amanullah,* Reshma Kewalaramani,† Hideo Yagita,‡ Terry B. Strom,* Mohamed H. Sayegh,† and Xian Chang Li*2 Blocking both CD28 and CD154 costimulatory pathways can induce transplant tolerance in some, but not all, transplant models.
    [Show full text]
  • Human CD Marker Chart Reviewed by HLDA1 Bdbiosciences.Com/Cdmarkers
    BD Biosciences Human CD Marker Chart Reviewed by HLDA1 bdbiosciences.com/cdmarkers 23-12399-01 CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD Alternative Name Ligands & Associated Molecules T Cell B Cell Dendritic Cell NK Cell Stem Cell/Precursor Macrophage/Monocyte Granulocyte Platelet Erythrocyte Endothelial Cell Epithelial Cell CD1a R4, T6, Leu6, HTA1 b-2-Microglobulin, CD74 + + + – + – – – CD93 C1QR1,C1qRP, MXRA4, C1qR(P), Dj737e23.1, GR11 – – – – – + + – – + – CD220 Insulin receptor (INSR), IR Insulin, IGF-2 + + + + + + + + + Insulin-like growth factor 1 receptor (IGF1R), IGF-1R, type I IGF receptor (IGF-IR), CD1b R1, T6m Leu6 b-2-Microglobulin + + + – + – – – CD94 KLRD1, Kp43 HLA class I, NKG2-A, p39 + – + – – – – – – CD221 Insulin-like growth factor 1 (IGF-I), IGF-II, Insulin JTK13 + + + + + + + + + CD1c M241, R7, T6, Leu6, BDCA1 b-2-Microglobulin + + + – + – – – CD178, FASLG, APO-1, FAS, TNFRSF6, CD95L, APT1LG1, APT1, FAS1, FASTM, CD95 CD178 (Fas ligand) + + + + + – – IGF-II, TGF-b latency-associated peptide (LAP), Proliferin, Prorenin, Plasminogen, ALPS1A, TNFSF6, FASL Cation-independent mannose-6-phosphate receptor (M6P-R, CIM6PR, CIMPR, CI- CD1d R3G1, R3 b-2-Microglobulin, MHC II CD222 Leukemia
    [Show full text]
  • Differential Signaling Via Tumor Necrosis Factor-Associated Factors (Trafs) by CD27 and CD40 in Mouse B Cells
    Differential Signaling via Tumor Necrosis Factor-Associated Factors (TRAFs) by CD27 and CD40 in Mouse B Cells So-Youn Woo1*, Hae-Kyung Park1 and Gail A. Bishop2,3,4 Department of Microbiology1, College of Medicine, Ewha Womans University, Seoul 158-710, Korea, Department of Microbiology2, and Department of Internal Medicine3, The University of Iowa, Veterans Affairs Medical Center4, Iowa City, IA 52242 ABSTRACT Background: CD27 is recently known as a memory B cell marker and is mainly ex- pressed in activated T cells, some B cell population and NK cells. CD27 is a member of tumor necrosis factor receptor family. Like CD40 molecule, CD27 has (P/S/T/A) X(Q/E)E motif for interacting with TNF receptor-associated factors (TRAFs), and TRAF2 and TRAF5 bindings to CD27 in 293T cells were reported. Methods: To investigate the CD27 signaling effect in B cells, human CD40 extracellular domain containing mouse CD27 cytoplamic domain construct (hCD40-mCD27) was transfected into mouse B cell line CH12.LX and M12.4.1. Results: Through the stimulation of hCD40-mCD27 molecule via anti-human CD40 antibody or CD154 ligation, expression of CD11a, CD23, CD54, CD70 and CD80 were increased and secretion of IgM was induced, which were comparable to the effect of CD40 stimulation. TRAF2 and TRAF3 were recruited into lipid-enriched membrane raft and were bound to CD27 in M12.4.1 cells. CD27 stimulation, however, did not increase TRAF2 or TRAF3 degradation. Conclusion: In contrast to CD40 signaling pathway, TRAF2 and TRAF3 degradation was not observed after CD27 stimulation and it might contribute to prolonged B cell activation through CD27 signaling.
    [Show full text]
  • Downloaded From
    Engagement of CD153 (CD30 Ligand) by CD30 + T Cells Inhibits Class Switch DNA Recombination and Antibody Production in Human IgD+ IgM+ B Cells This information is current as of September 26, 2021. Andrea Cerutti, Andràs Schaffer, Raymond G. Goodwin, Shefali Shah, Hong Zan, Scott Ely and Paolo Casali J Immunol 2000; 165:786-794; ; doi: 10.4049/jimmunol.165.2.786 http://www.jimmunol.org/content/165/2/786 Downloaded from References This article cites 72 articles, 42 of which you can access for free at: http://www.jimmunol.org/content/165/2/786.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 26, 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 © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Engagement of CD153 (CD30 Ligand) by CD30؉ T Cells Inhibits Class Switch DNA Recombination and Antibody Production in Human IgD؉ IgM؉ B Cells1 Andrea Cerutti,2* Andràs Schaffer,*† Raymond G.
    [Show full text]
  • Activation of CD40 with Platelet Derived CD154 Promotes Reactive Oxygen Species Dependent Death of Human Hepatocytes During Hypoxia and Reoxygenation
    Activation of CD40 with Platelet Derived CD154 Promotes Reactive Oxygen Species Dependent Death of Human Hepatocytes during Hypoxia and Reoxygenation Ricky H. Bhogal*, Christopher J. Weston, Stuart M. Curbishley, David H. Adams, Simon C. Afford Centre for Liver Research, School of Infection and Immunity, Institute of Biomedical Research, The Medical School, The University of Birmingham, Edgbaston, Birmingham, United Kingdom Abstract Background: Hypoxia and hypoxia-reoxygenation (H-R) are pathogenic factors in many liver diseases that lead to hepatocyte death as a result of reactive oxygen species (ROS) accumulation. The tumor necrosis factor super-family member CD154 can also induce hepatocyte apoptosis via activation of its receptor CD40 and induction of autocrine/paracrine Fas Ligand/CD178 but the relationship between CD40 activation, ROS generation and apoptosis is poorly understood. We hypothesised that CD40 activation and ROS accumulation act synergistically to drive human hepatocyte apoptosis. Methods: Human hepatocytes were isolated from liver tissue and exposed to an in vitro model of hypoxia and H-R in the presence or absence of CD154 and/or various inhibitors. Hepatocyte ROS production, apoptosis and necrosis were determined by labelling cells with 29,79-dichlorofluorescin, Annexin-V and 7-AAD respectively in a three-colour reporter flow cytometry assay. Results: Exposure of human hepatocytes to recombinant CD154 or platelet-derived soluble CD154 augments ROS accumulation during H-R resulting in NADPH oxidase-dependent apoptosis and necrosis. The inhibition of c-Jun N-terminal Kinase and p38 attenuated CD154-mediated apoptosis but not necrosis. Conclusions: CD154-mediated apoptosis of hepatocytes involves ROS generation that is amplified during hypoxia- reoxygenation.
    [Show full text]
  • Mechanism CD40-Dependent Cytolytic − Novel CD154
    Vaccination Produces CD4 T Cells with a Novel CD154−CD40-Dependent Cytolytic Mechanism This information is current as Rhea N. Coler, Thomas Hudson, Sean Hughes, Po-wei D. of October 1, 2021. Huang, Elyse A. Beebe and Mark T. Orr J Immunol published online 21 August 2015 http://www.jimmunol.org/content/early/2015/08/20/jimmun ol.1501118 Downloaded from Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision http://www.jimmunol.org/ • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: by guest on October 1, 2021 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 © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published August 21, 2015, doi:10.4049/jimmunol.1501118 The Journal of Immunology Vaccination Produces CD4 T Cells with a Novel CD154–CD40-Dependent Cytolytic Mechanism Rhea N. Coler,*,†,‡ Thomas Hudson,* Sean Hughes,* Po-wei D. Huang,* Elyse A. Beebe,* and Mark T. Orr*,† The discovery of new vaccines against infectious diseases and cancer requires the development of novel adjuvants with well-defined activities.
    [Show full text]
  • Improving Treatment of Infectious Diseases
    2 WISSENSCHAFT | SCIENCE DBM Hebelstrasse Improving treatment of infectious diseases The Infection Biology research group explores host- Infections in immunocompromised patients are and pathogen-specific aspects of infectious diseases common in a translational setting together with the Division Chemotherapies to treat leukemia and solid tumors and of Infectious Diseases and Hospital Epidemiology, immunosuppressive treatments to reduce graft versus the Laboratory of Clinical Microbiology, the Division host diseases (GVHD) and rejection in transplant recipi- of Hematology at the University Hospital Basel, the ents have overall increased the short and mid-term sur- Biozentrum, ETH Zürich and Basel and the University vival of these patients. However, the loss of pathogen- of Fribourg. Our laboratory has two main topics: First, specific immunity associated with these treatments we aim at understanding and improving the host im- increases the risk for infectious complications. Invasive mune response towards viruses and fungi in immu- fungal and viral infections belong to the most serious nocompromised patients. This also includes vaccine complications in these patients and are still associated responses 1-5. The second goal is to explore novel anti- with an exuberant mortality. Although antifungal and infective approaches against foreign-body/implant- antiviral drugs are available for some infections, their associated infections caused by staphylococci 6,7. therapeutic efficacy is often limited and depends on several factors including the immune status of the host In this report, we focus on infections in immunocom- and the extent of infection at the time of diagnosis. Due promised patients, the host immune response to to the disease severity in these patients and the problem fungal infections, as well as pre-clinical and clinical of accurate diagnosis, efforts have been made to imple- studies of adoptive T-cell therapy for fungal and viral ment prophylactic and preemptive drugs.
    [Show full text]