DOCSLIB.ORG

And Memory Response Post-Germinal Center B Cell

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
And Memory Response Post-Germinal Center B Cell Role of MHC Class II on Memory B Cells in Post-Germinal Center B Cell Homeostasis and Memory Response This information is current as Michiko Shimoda, Tao Li, Jeanene P. S. Pihkala and of September 27, 2021. Pandelakis A. Koni J Immunol 2006; 176:2122-2133; ; doi: 10.4049/jimmunol.176.4.2122 http://www.jimmunol.org/content/176/4/2122 Downloaded from References This article cites 56 articles, 32 of which you can access for free at: http://www.jimmunol.org/content/176/4/2122.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 27, 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 © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Role of MHC Class II on Memory B Cells in Post-Germinal Center B Cell Homeostasis and Memory Response1 Michiko Shimoda,2*† Tao Li,* Jeanene P. S. Pihkala,* and Pandelakis A. Koni2*‡ We investigated the role of B cell Ag presentation in homeostasis of the memory B cell compartment in a mouse model where a conditional allele for the ␤-chain of MHC class II (MHC-II) is deleted in the vast majority of all B cells by cd19 promoter-mediated expression of Cre recombinase (IA-B mice). Upon T cell-dependent immunization, a small number of MHC-II؉ B cells in IA-B mice dramatically expanded and restored normal albeit delayed levels of germinal center (GC) B cells with an affinity-enhancing somatic mutation to Ag. IA-B mice also established normal levels of MHC-II؉ memory B cells, which, however, subsequently lost MHC-II expression by ongoing deletion of the conditional iab allele without significant loss in their number. Furthermore, in vivo Ag restimulation of MHC-II؊ memory B cells of IA-B mice failed to cause differentiation into plasma cells (PCs), even in the ؉ presence of Ag-specific CD4 T cells. In addition, both numbers and Ag-specific affinity of long-lived PCs during the late post-GC Downloaded from phase, as well as post-GC serum affinity maturation, were significantly reduced in IA-B mice. These results support a notion that MHC-II-dependent T cell help during post-GC phase is not absolutely required for the maintenance of memory B cell frequency but is important for their differentiation into PCs and for the establishment of the long-lived PC compartment. The Journal of Immunology, 2006, 176: 2122–2133. 3 ajor histocompatibility complex class II (MHC-II) - lived PCs are long-lived (8, 9) and can be maintained without http://www.jimmunol.org/ restricted B cell Ag presentation is essential for the immunizing Ag persistence (10–12). Other studies also suggested M induction of Ag-specific humoral immune response that memory B cells were maintained in mice deprived of CD4ϩ T and generation of immunological memory. Upon infection or im- cells (13) or in mice deficient in complement receptor 2 (Cr2) (14). munization with T cell-dependent (TD) Ag, Ag-specific B cells Furthermore, recent studies have shown that polyclonal stimula- ϩ present Ag to Ag-specific CD4 T cells primed by dendritic cells tion such as CpG DNA or bystander T cell help can provide pro- (DCs), and this cognate T cell-B cell interaction promotes B cell liferation and even differentiation of memory B cells (11, 12). In proliferation and differentiation either into extrafollicular plasma addition, virus-specific memory B cells can be activated and dif- cells (PCs) or germinal center (GC) B cells (1, 2). During ensuing ferentiated into PCs in the absence of CD4ϩ T cells (15). Thus, massive proliferation, GC B cells undergo somatic mutations in the these studies support a notion that established memory B cells are by guest on September 27, 2021 V region of their Ig BCR, which can change the affinity of the BCR mainly maintained independent of Ag itself or Ag-specific T cell to Ag. High-affinity B cells survive by preferential interaction with help, and their differentiation into PCs is CD4ϩ T cell independent. follicular DCs and T cells, while low-affinity B cells die by apoptosis In contrast, there are also findings suggesting that even long-lived (3). This GC selection process is responsible for the generation of PCs are replenished by differentiation of high-affinity precursors “non-Ab-secreting” memory B cells and “Ab-secreting” long-lived during the post-GC phase, reflected in post-GC serum Ig affinity PCs in bone marrow (BM) (4), both of which are necessary for long- maturation, which itself is dependent on Ag-deposition (5, 16–20). term immunological memory and protection (4–6). Irradiated Cr2Ϫ/Ϫ chimeric mice reconstituted with Ag-primed B In contrast to the extensive studies on GC B cell differentiation cells and T cells showed reduced frequency of memory B cells and and selection, the mechanisms delineating memory B cells and long-lived PCs from GC B cells and the maintenance of these two Ab-secreting cells (ASCs) (19). In addition, post-GC B cells failed B cell populations long after their generation are largely unknown. to induce Blimp-1, XBP-1, and Bcl-2, which resulted in failure to Previous studies revealed that both memory B cells (7) and long- generate the precursor population of long-lived PCs (14). These results strongly suggest that there is an Ag-dependent mechanism for the maintenance of long-lived PC compartment by differenti- *Program in Molecular Immunology, Immunotherapy Center, †Department of Pathol- ation of precursors, which is required for the maximum retention ‡ ogy, and Department of Medicine, Medical College of Georgia, Augusta, GA 30912 of long-term protective humoral immunity. Received for publication August 17, 2005. Accepted for publication November Classically, Ag-specific B220ϩ memory B cells are defined as 25, 2005. class-switched IgDϪIgMϪ B cells (21, 22) and highly express 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 CD38 (23, 24). However, several other studies now also show that with 18 U.S.C. Section 1734 solely to indicate this fact. Ag restimulation promotes B220ϩCD138Ϫ memory B cells to Ϫ Ϫ 1 This work was supported in part by Medical College of Georgia Combined Intra- generate B220 CD138 preplasma memory B cells that are also mural Grants Program grants-in-aid (to M.S. and P.A.K.). maintained in the post-GC phase and differentiate into PCs upon 2 Address correspondence and reprint requests to Dr. Michiko Shimoda or Dr. Pan- Ag recall (6, 25, 26). In addition, by using a transgenic BCR delakis A. Koni, Program in Molecular Immunology, Immunotherapy Center, De- partment of Medicine, Medical College of Georgia, 1120, 15th Street, Augusta, GA model, precursors for long-lived PCs were identified in BM, which 30912. E-mail address: [email protected] or [email protected] proliferate and differentiate into PCs in the absence of Ag (18). It 3 Abbreviations used in this paper: MHC-II, MHC class II; PC, plasma cell; GC, is not clear at present whether memory B cells and long-lived PCs germinal center; CGG, chicken gammaglobulin; NP, (4-hydroxy-3-nitrophenyl)ac- etyl; ASC, Ab-secreting cell; TD, T cell dependent; TI, T cell independent; BM, bone are largely maintained independently as a separate compartment marrow. once derived from GC B cells (4) or whether, in fact, these B cell Copyright © 2006 by The American Association of Immunologists, Inc. 0022-1767/06/$02.00 The Journal of Immunology 2123 subsets in the post-GC B cell compartment sequentially or inde- 6.7), CD90.1 (HIS51), TCR␤ (H57-597), CD19 (1D3), CD138 (281-2), pendently act as precursors of long-lived PCs (6). To support the 120G8 (Ref. 32; provided by Dr. G. Trinchieri, Schering-Plough Research ␣b latter, it has been suggested that virus-specific long-term Ab mem- Institute, Kenilworth, NJ), IA (Y3P; provided by our colleague Dr. L. ϩ Ignatowicz, Medical College of Georgia, Augusta, GA), and PNA-FITC ory is provided by Ag-driven and CD4 TD continuous differen- (Vector Laboratories). Abs were from BD Biosciences unless otherwise tiation of memory B cells into short-lived PCs (20). Therefore, indicated. NP-haptenated PE (NP20-PE) was prepared as described else- these post-GC B cells are considered to be points of selection of where (31). Cells were analyzed on a FACSCalibur (BD Biosciences) with high-affinity clones responsible for post-GC serum affinity matu- CellQuest software (BD Biosciences). Ag-specific GC B cells and B220ϩ memory B cells were identified by ration, and their terminal differentiation into PCs is controlled by five-color analysis as previously reported (33, 34). Briefly, cells were certain mechanisms to achieve maximal affinity in the long-lived stained on ice for 45 min with a mixture of biotinylated specific Abs to PC compartment. IgM, IgD, CD43 (S7), CD5, Gr-1 (RB6-8C5), CD11b, CD49b (DX5), and In this article, we study the role of MHC-II-restricted B cell Ag CD90.2 (30-H12) to exclude naive B cells, PCs, B-1 cells, macrophages, presentation for memory B cell maintenance and their terminal NK T cells, and T cells (lineage depletion Ab mixture).
Load more

Recommended publications
  • CD38, CD157, and RAGE As Molecular Determinants for Social Behavior
    cells Review CD38, CD157, and RAGE as Molecular Determinants for Social Behavior Haruhiro Higashida 1,2,* , Minako Hashii 1,3, Yukie Tanaka 4, Shigeru Matsukawa 5, Yoshihiro Higuchi 6, Ryosuke Gabata 1, Makoto Tsubomoto 1, Noriko Seishima 1, Mitsuyo Teramachi 1, Taiki Kamijima 1, Tsuyoshi Hattori 7, Osamu Hori 7 , Chiharu Tsuji 1, Stanislav M. Cherepanov 1 , Anna A. Shabalova 1, Maria Gerasimenko 1, Kana Minami 1, Shigeru Yokoyama 1, Sei-ichi Munesue 8, Ai Harashima 8, Yasuhiko Yamamoto 8, Alla B. Salmina 1,2 and Olga Lopatina 2 1 Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa University, Kanazawa 920-8640, Japan; [email protected] (M.H.); [email protected] (R.G.); [email protected] (M.T.); [email protected] (N.S.); [email protected] (M.T.); [email protected] (T.K.); [email protected] (C.T.); [email protected] (S.M.C.); [email protected] (A.A.S.); [email protected] (M.G.); minami-k@staff.kanazawa-u.ac.jp (K.M.); [email protected] (S.Y.) 2 Laboratory of Social Brain Study, Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia; [email protected] (A.B.S.); [email protected] (O.L.) 3 Division of Molecular Genetics and Clinical Research, National Hospital Organization Nanao Hospital, Nanao 926-0841, Japan 4 Molecular Biology and Chemistry, Faculty of Medical Science, University of Fukui, Fukui
    [Show full text]
  • Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE
    International Journal of Molecular Sciences Article Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE Marie Burns 1,†, Lennard Ostendorf 1,2,3,† , Robert Biesen 1,2 , Andreas Grützkau 1, Falk Hiepe 1,2, Henrik E. Mei 1,† and Tobias Alexander 1,2,*,† 1 Deutsches Rheuma-Forschungszentrum (DRFZ Berlin), a Leibniz Institute, 10117 Berlin, Germany; [email protected] (M.B.); [email protected] (L.O.); [email protected] (R.B.); [email protected] (A.G.); [email protected] (F.H.); [email protected] (H.E.M.) 2 Department of Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and The Berlin Institute of Health (BIH), 10117 Berlin, Germany 3 Department of Nephrology and Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and The Berlin Institute of Health (BIH), 10117 Berlin, Germany * Correspondence: [email protected] † Authors contributed equally to this manuscript. Abstract: Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, Citation: Burns, M.; Ostendorf, L.; and with clinical and serologic disease parameters of SLE.
    [Show full text]
  • Immunity ≠ Immunological Memory
    Immunity ≠ Immunological Memory Rolf Zinkernagel University of Zurich IMI Stakeholder Forum - 13 May 2013 - Brussels • Protective vaccines imitate co-evolution of infectious agents and hosts. • We cannot do better than evolution by using the same tools, only when introducing ‘new’ tools (antibiotics, antivirals, autoantibodies, behavioural changes) • Vaccines against solid tumours (carcinomas, sarcomas) and chronic persistent infections are theoretically not impossible but practically highly unlikely! Vaccines Not successful available Polio 1, 2, 3 TB bact. toxins Leprosy measles HIV Haem. infl. malaria (cholera) Neutr. / effector T cells opsonising antibodies antibodies igG (IgA) IMMUNITY • "innate resistance" > 95 % • Ab in eggs • protective memory via Ab (vaccines) • TB: no vaccine • autoimmunity > 30 y, female > male 5 : 1 • tumors > 30 years • Is what we measure biologically important ? (e.g. acad. memory: earlier + greater) CTL ELISA nAb Immunity Immunology Protection • ‚Memory‘ • Small pox • quicker - higher • Poliomeningitis • Measles • HIV, malaria - • Tuberculosis ± Antibody Memory after immunization with VSV a) neutralizing antibodies b) ELISA 12 12 ) 10 ) 10 2 3 8 8 40 log 10 log 6 - - 6 NP binding NP - 4 IND neutralizing 4 - IgG ( IgG ( 2 VSV 2 VSV 0 0 0 20 100 200 300 0 20 100 200 300 days after immunization days after immunization Why immunological Memory ? Protection (immunity) counts ! • Earlier + better • If first infection survived no need for memory • If first infection kills no need for memory • All vaccines that
    [Show full text]
  • CD Markers Are Routinely Used for the Immunophenotyping of Cells
    ptglab.com 1 CD MARKER ANTIBODIES www.ptglab.com Introduction The cluster of differentiation (abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules. So-called CD markers are routinely used for the immunophenotyping of cells. Despite this use, they are not limited to roles in the immune system and perform a variety of roles in cell differentiation, adhesion, migration, blood clotting, gamete fertilization, amino acid transport and apoptosis, among many others. As such, Proteintech’s mini catalog featuring its antibodies targeting CD markers is applicable to a wide range of research disciplines. PRODUCT FOCUS PECAM1 Platelet endothelial cell adhesion of blood vessels – making up a large portion molecule-1 (PECAM1), also known as cluster of its intracellular junctions. PECAM-1 is also CD Number of differentiation 31 (CD31), is a member of present on the surface of hematopoietic the immunoglobulin gene superfamily of cell cells and immune cells including platelets, CD31 adhesion molecules. It is highly expressed monocytes, neutrophils, natural killer cells, on the surface of the endothelium – the thin megakaryocytes and some types of T-cell. Catalog Number layer of endothelial cells lining the interior 11256-1-AP Type Rabbit Polyclonal Applications ELISA, FC, IF, IHC, IP, WB 16 Publications Immunohistochemical of paraffin-embedded Figure 1: Immunofluorescence staining human hepatocirrhosis using PECAM1, CD31 of PECAM1 (11256-1-AP), Alexa 488 goat antibody (11265-1-AP) at a dilution of 1:50 anti-rabbit (green), and smooth muscle KD/KO Validated (40x objective). alpha-actin (red), courtesy of Nicola Smart. PECAM1: Customer Testimonial Nicola Smart, a cardiovascular researcher “As you can see [the immunostaining] is and a group leader at the University of extremely clean and specific [and] displays Oxford, has said of the PECAM1 antibody strong intercellular junction expression, (11265-1-AP) that it “worked beautifully as expected for a cell adhesion molecule.” on every occasion I’ve tried it.” Proteintech thanks Dr.
    [Show full text]
  • The Enzymatic Activities of CD38 Enhance CLL Growth and Trafficking
    Leukemia (2015) 29, 356–368 © 2015 Macmillan Publishers Limited All rights reserved 0887-6924/15 www.nature.com/leu ORIGINAL ARTICLE The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting T Vaisitti1,2, V Audrito1,2, S Serra1,2, R Buonincontri1,2, G Sociali3, E Mannino3, A Pagnani2, A Zucchetto4, E Tissino4, C Vitale5, M Coscia5, C Usai6, C Pepper7, V Gattei4, S Bruzzone3 and S Deaglio1,2 The ecto-enzyme CD38 is gaining momentum as a novel therapeutic target for patients with hematological malignancies, with several anti-CD38 monoclonal antibodies in clinical trials with promising results. In chronic lymphocytic leukemia (CLL) CD38 is a marker of unfavorable prognosis and a central factor in the pathogenetic network underlying the disease: activation of CD38 regulates genetic pathways involved in proliferation and movement. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme-deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD into ADPR (ADP-ribose) and cADPR (cyclic ADP-ribose), CD38 increases cytoplasmic Ca2+ concentrations, positively influencing proliferation and signaling mediated via chemokine receptors or integrins. Consistently, inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL chemotaxis, adhesion and in vivo homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, thereby increasing responses to chemotherapy. These results suggest that monoclonal antibodies that block the enzymatic activities of CD38 or enzyme inhibitors may prove therapeutically useful.
    [Show full text]
  • Monoclonal Antibodies in Myeloma
    Monoclonal Antibodies in Myeloma Pia Sondergeld, PhD, Niels W. C. J. van de Donk, MD, PhD, Paul G. Richardson, MD, and Torben Plesner, MD Dr Sondergeld is a medical student at the Abstract: The development of monoclonal antibodies (mAbs) for University of Giessen in Giessen, Germany. the treatment of disease goes back to the vision of Paul Ehrlich in Dr van de Donk is a hematologist in the the late 19th century; however, the first successful treatment with department of hematology at the VU a mAb was not until 1982, in a lymphoma patient. In multiple University Medical Center in Amsterdam, The Netherlands. Dr Richardson is the R.J. myeloma, mAbs are a very recent and exciting addition to the Corman Professor of Medicine at Harvard therapeutic armamentarium. The incorporation of mAbs into Medical School, and clinical program current treatment strategies is hoped to enable more effective and leader and director of clinical research targeted treatment, resulting in improved outcomes for patients. at the Jerome Lipper Myeloma Center, A number of targets have been identified, including molecules division of hematologic malignancy, depart- on the surface of the myeloma cell and components of the bone ment of medical oncology, Dana-Farber Cancer Institute in Boston, MA. Dr Plesner marrow microenvironment. Our review focuses on a small number is a professor of hematology at the Univer- of promising mAbs directed against molecules on the surface of sity of Southern Denmark and a consultant myeloma cells, including CS1 (elotuzumab), CD38 (daratumumab, in the department of hematology at Vejle SAR650984, MOR03087), CD56 (lorvotuzumab mertansine), and Hospital in Vejle, Denmark.
    [Show full text]
  • NK Cells Remember
    Sweet Is the Memory of Past Troubles: NK Cells Remember Deborah W. Hendricks, Gundula Min-Oo and Lewis L. Lanier Abstract Natural killer (NK) cells are important in host defense against tumors and microbial pathogens. Recent studies indicate that NK cells share many features with the adaptive immune system, and like B cells and T cells, NK cells can acquire immunological memory. Here, we review evidence for NK cell memory and the molecules involved in the generation and maintenance of these self-renewing NK cells that provide enhanced protection of the host. Contents 1 Introduction.............................................................................................................................. 2 Antigen-Specific Recall Responses in a Contact Hypersensitivity Model............................. 2.1 Hepatic NK Cells Acquire Memory to Haptens and Viruslike Particles ...................... 2.2 Insights into the Mechanism of NK Cell Memory in Contact Hypersensitivity and Skin Inflammation ................................................................................................... 3 The Development of NK Cell Memory in Chronic Viral Infections..................................... 3.1 NK Cell Memory Following Mouse Cytomegalovirus Infection .................................. 3.2 NK Cell Memory Following Human Cytomegalovirus Infection ................................. 3.3 Antibody-Dependent Memory-Like NK Cells ............................................................... 3.4 Specificity of NK Cell Memory in Mice and Humans.................................................
    [Show full text]
  • A Molecular Signature of Dormancy in CD34+CD38- Acute Myeloid Leukaemia Cells
    www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 67), pp: 111405-111418 Research Paper A molecular signature of dormancy in CD34+CD38- acute myeloid leukaemia cells Mazin Gh. Al-Asadi1,2, Grace Brindle1, Marcos Castellanos3, Sean T. May3, Ken I. Mills4, Nigel H. Russell1,5, Claire H. Seedhouse1 and Monica Pallis5 1University of Nottingham, School of Medicine, Academic Haematology, Nottingham, UK 2University of Basrah, College of Medicine, Basrah, Iraq 3University of Nottingham, School of Biosciences, Nottingham, UK 4Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK 5Clinical Haematology, Nottingham University Hospitals, Nottingham, UK Correspondence to: Claire H. Seedhouse, email: [email protected] Keywords: AML; dormancy; gene expression profiling Received: September 19, 2017 Accepted: November 14, 2017 Published: November 30, 2017 Copyright: Al-Asadi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Dormant leukaemia initiating cells in the bone marrow niche are a crucial therapeutic target for total eradication of acute myeloid leukaemia. To study this cellular subset we created and validated an in vitro model employing the cell line TF- 1a, treated with Transforming Growth Factor β1 (TGFβ1) and a mammalian target of rapamycin inhibitor. The treated cells showed decreases in total RNA, Ki-67 and CD71, increased aldehyde dehydrogenase activity, forkhead box 03A (FOX03A) nuclear translocation and growth inhibition, with no evidence of apoptosis or differentiation. Using human genome gene expression profiling we identified a signature enriched for genes involved in adhesion, stemness/inhibition of differentiation and tumour suppression as well as canonical cell cycle regulation.
    [Show full text]
  • Human Antigen-Specific Memory Natural Killer Cell Responses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.11.09.374348; this version posted November 10, 2020. 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 Human antigen-specific memory natural killer cell responses develop 2 against HIV-1 and influenza virus and are dependent on MHC-E 3 restriction 4 5 6 Stephanie Jost1, Olivier Lucar1, Taylor Yoder1, Kyle Kroll1, Sho Sugawara1, Scott Smith1, Rhianna 7 Jones1, George Tweet1, Alexandra Werner1, Phillip J. Tomezsko2, Haley L. Dugan2†, Joshua 1 3 3 4 5 8 Ghofrani , Marcus Altfeld , Adam Grundhoff , Michaela Muller-Trutwin , Paul Goepfert , R. Keith 9 Reeves1,2 * 10 11 1Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard 12 Medical School, Boston, MA 02115, USA; 2Ragon Institute of Massachusetts General Hospital, 13 MIT, and Harvard, Cambridge, MA 02139, USA; 3Heinrich Pette Institute, Leibniz Institute for 14 Experimental Virology, 20251 Hamburg, Germany; 4Institut Pasteur, HIV, Inflammation and 15 Persistence Unit, Paris, France; 5University of Alabama at Birmingham, Birmingham, AL 35294, 16 USA 17 18 *Corresponding author 19 R. Keith Reeves 20 Center for Virology and Vaccine Research 21 Beth Israel Deaconess Medical Center 22 3 Blackfan Circle 23 Boston, MA 02215 24 Ph: (617-735-4586) 25 Fax: (617-735-4527) 26 E-mail: [email protected] 27 28 †Current address: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA 29 30 Running Title: Human Memory NK Cells 31 32 Abstract: 185 words 33 Main Text: 2713 words 34 Methods Text: 2035 words 35 5 Figures 36 7 Supplemental Figures 37 3 Supplemental Tables 38 62 references 39 40 bioRxiv preprint doi: https://doi.org/10.1101/2020.11.09.374348; this version posted November 10, 2020.
    [Show full text]
  • ADP-Ribose Or Cyclic ADP-Ribose Independently of Enzymatically
    CD38 Signaling in B Lymphocytes Is Controlled by Its Ectodomain but Occurs Independently of Enzymatically Generated ADP-Ribose or Cyclic ADP-Ribose This information is current as of September 27, 2021. Frances E. Lund, Hélène M. Muller-Steffner, Naixuan Yu, C. David Stout, Francis Schuber and Maureen C. Howard J Immunol 1999; 162:2693-2702; ; http://www.jimmunol.org/content/162/5/2693 Downloaded from References This article cites 39 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/162/5/2693.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 27, 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 © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. CD38 Signaling in B Lymphocytes Is Controlled by Its Ectodomain but Occurs Independently of Enzymatically Generated ADP-Ribose or Cyclic ADP-Ribose1 Frances E. Lund,2*He´le`ne M. Muller-Steffner,† Naixuan Yu,* C.
    [Show full text]
  • The Functional in Vitro Response to CD40 Ligation Reflects a Different
    Leukemia (2011) 25, 1760–1767 & 2011 Macmillan Publishers Limited All rights reserved 0887-6924/11 www.nature.com/leu ORIGINAL ARTICLE The functional in vitro response to CD40 ligation reflects a different clinical outcome in patients with chronic lymphocytic leukemia This article has been corrected since advance Online Publication, and a corrigendum is also printed in this issue C Scielzo1,2,9, B Apollonio1,3,4,9, L Scarfo` 5,6, A Janus6, M Muzio1,4, E ten Hacken3,6, P Ghia3,6,7,8 and F Caligaris-Cappio1,3,7,8 1Laboratory of Lymphoid Malignancies, Division of Molecular Oncology, Istituto Scientifico San Raffaele, Milan, Italy; 2Unversita` degli studi di Milano, Milan, Italy; 3Universita` Vita-Salute San Raffaele, Milan, Italy; 4Laboratory of cell activation and signalling, Division of Molecular Oncology, Istituto Scientifico San Raffaele, Milan, Italy; 5Haematology Section, University of Ferrara, Ferrara, Italy; 6Laboratory of B Cell Neoplasia, Division of Molecular Oncology, Istituto Scientifico San Raffaele, Milan, Italy; 7Unit of Lymphoid Malignancies, Department of Oncology, Istituto Scientifico San Raffaele, Milan, Italy and 8MAGIC (Microenvironment and Genes in Cancers of the blood) Interdivisional Research Program, Istituto Scientifico San Raffaele, Milan, Italy Malignant B lymphocytes from chronic lymphocytic leukemia who have a poorer clinical outcome and tend to express other (CLL) patients maintain the capacity to respond to CD40 negative prognostic factors (for example, ZAP70 or CD38 ligation, among other microenvironmental stimuli.
    [Show full text]
  • NK Cell Responses Redefine Immunological Memory
    Th eJournal of Brief Reviews Immunology NK Cell Responses Redefine Immunological Memory Nicholas M. Adams,* Timothy E. O’Sullivan,* Clair D. Geary,* Jenny M. Karo,* Robert A. Amezquita,† Nikhil S. Joshi,† Susan M. Kaech,† and Joseph C. Sun*,‡ Immunological memory has traditionally been regarded theAg-specificnatureoftheseAbtiters(5).Thelampreycan as a unique trait of the adaptive immune system. Nev- also mediate delayed-type hypersensitivity reactions follow- ertheless, there is evidence of immunological memory in ing stimulation with Mycobacterium tuberculosis–fortified lower organisms and invertebrates, which lack an adap- CFA (5). The basis for these phenomena may be attributable tive immune system. Despite their innate ability to rap- to the recently discovered lymphocyte-like populations and idly produce effector cytokines and kill virally infected or variable lymphocyte receptors, akin to primordial T and transformed cells, NK cells also exhibit adaptive charac- B lymphocytes and their Ag receptors, respectively (6, 7). teristics such as clonal expansion, longevity, self-renewal, However, evidence also exists for immunological memory in and robust recall responses to antigenic or nonantigenic invertebrates devoid of an adaptive immune system. Protection stimuli. In this review, we highlight the intracellular and of the American cockroach Periplaneta americana against the extracellular requirements for memory NK cell genera- bacterium Pseudomonas aeruginosa was enhanced by prior immunization with killed P. aeruginosa but not with saline or tion and describe the emerging evidence for memory pre- immunization with an array of other Gram-negative organ- cursor NK cells and their derivation. The Journal of isms (8). Interestingly, this protection against P. aeruginosa Immunology, 2016, 197: 2963–2970.
    [Show full text]