DOCSLIB.ORG

Lymphopoiesis Prebcr-Dependent Events During B Phosphorylation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lymphopoiesis Prebcr-Dependent Events During B Phosphorylation Heparan Sulfate and Heparin Enhance ERK Phosphorylation and Mediate preBCR-Dependent Events during B Lymphopoiesis This information is current as of September 29, 2021. Craig D. Milne, Steven A. Corfe and Christopher J. Paige J Immunol 2008; 180:2839-2847; ; doi: 10.4049/jimmunol.180.5.2839 http://www.jimmunol.org/content/180/5/2839 Downloaded from References This article cites 30 articles, 16 of which you can access for free at: http://www.jimmunol.org/content/180/5/2839.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 29, 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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Heparan Sulfate and Heparin Enhance ERK Phosphorylation and Mediate preBCR-Dependent Events during B Lymphopoiesis1 Craig D. Milne,2 Steven A. Corfe, and Christopher J. Paige As B lineage cells develop, they interact with cells, proteins, and extracellular matrix components of the surrounding microen- vironment. In vitro, one critical checkpoint for developing cells occurs as they lose responsiveness to IL-7. These cells require contact with either stromal cells or other B lineage cells to mature. Our results demonstrate that heparan sulfate and heparin are able to promote this transition when added exogenously to the culture system or when heparan sulfate-bearing cell lines are cocultured with primary B cell progenitors. Addition of heparan sulfate or heparin to LPS-stimulated cultures of primary B cell progenitors resulted in more IgM secreted compared with untreated cultures. Heparan sulfate has been Downloaded from reported to be a ligand for the pre-B cell receptor (preBCR). Extending this observation, we found that treatment of ,preBCR؉ cells with heparan sulfate before anti-␮ stimulation leads to increased phosphorylation of ERK1/2. Consequently -preBCR؉ cells proliferate more in the presence of IL-7 and heparan sulfate, whereas preBCR؊ cells are unaffected, sug gesting that in these experiments, heparan sulfate is not directly affecting IL-7 activity. Heparin treatment of cultures induces .many of the same biological effects as treatment with heparan sulfate, including elevated pERK levels in preBCR؉ cells However, heparin reduces the proliferation of cells expressing only the preBCR (opposed to both the preBCR and BCR) http://www.jimmunol.org/ possibly due to internalization of the preBCR. Heparan sulfates are present on stromal cells and B lineage cells present in hemopoietic tissues and may provide stimulation to preB cells testing the signaling capacity of the preBCR. The Journal of Immunology, 2008, 180: 2839–2847. he development of B lineage cells depends on the inte- port of this, Ja¨ck and colleagues (10, 11) developed a soluble gration of signals from several biochemical pathways. preBCR-like molecule and found that it could bind to an uniden- Prominent among these are pathways linked to the pre-B tified 90–135 kDa protein in stromal cell lysates. This interaction T 3 cell receptor (preBCR) and the IL-7R, however, contributions requires the unique tail of ␭5, which interacts with heparan sulfate from accessory molecules such as CD19, CD22, CD45, and others chains associated with this protein. by guest on September 29, 2021 can alter the signaling milieu and influence the development of B We have previously described a culture system that allows for lineage cells (1, 2). The central importance of the preBCR has been the maturation of B cell progenitors from lineage uncommitted recognized for many years and is most easily demonstrated in ex- cells through to the IgM-secreting mature B cell stage (12–14). perimental systems that are either deficient in one or more com- Consequently, this culture system supports any required signaling ponents of the preBCR or in systems that artificially mimic pre- by the preBCR or other receptors necessary to mediate this mat- BCR-dependent signaling (3–5). uration. Ig-secreting B lineage cells can be generated in vitro from Despite these observations, the precise mechanism by which the ϩ B220 bone marrow progenitors by culturing cells under a series preBCR influences B cell development remains elusive and a num- of different conditions. Early phases require IL-7 for proliferation, ber of models have been proposed (6–8). At one extreme, it is survival, and maturation of progenitor cells; however, to reach the thought that simple assembly of preBCR components is sufficient Ig-secreting stage in vitro, cells must be transferred to cultures to generate critical signals that promote development. Others pos- containing LPS. This transition phase is not well understood, but tulate that receptor engagement is needed to initiate signal trans- duction and a number of ligands have been proposed (9). In sup- has classically required a coculture period between stromal cells and B lineage progenitors (15). This coculture permits B lineage cells to mature to the LPS-responsive stage and, ultimately, secrete Ig. In the absence of this contact-dependent stage, cells do not Ontario Cancer Institute, University Health Network, Department of Immunology, University of Toronto, Toronto, Ontario, Canada respond to LPS and do not secrete Ig. Stromal cells produce many Received for publication August 15, 2007. Accepted for publication December cytokines, growth factors, and adhesion molecules, but it is unclear 17, 2007. which specific molecules are necessary to mediate the maturation The costs of publication of this article were defrayed in part by the payment of page of B lineage cells at this stage. charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. One model suggests that an important stimulus for develop- 1 ing B lineage cells is the loss of IL-7 availability. This has been This work was supported by grants from the Terry Fox Foundation, the National ϩ Cancer Institute of Canada, and the Canadian Institute of Health Research. reported to induce maturation of pre-B cells to the sIgM stage; 2 Address correspondence and reprint requests to Dr. Craig Milne, Ontario Cancer however, we have previously shown this not to be true (16). The Institute, 8-105 Princess Margaret Hospital, Toronto, Ontario, Canada M5G 2M9. loss of IL-7 does not change the number of cells reaching the E-mail address: [email protected] sIgMϩ stage; it merely changes the proportion of cells surviving in 3 Abbreviations used in this paper: preBCR, pre-B cell receptor. culture, to favor more sIgMϩ cells at the expense of sIgMϪ pro-B Copyright © 2008 by The American Association of Immunologists, Inc. 0022-1767/08/$2.00 and pre-B cells. Although possibly acting upon similar cells, the www.jimmunol.org 2840 HEPARAN SULFATE AND HEPARIN MEDIATE preBCR-DEPENDENT EVENTS contact-dependent interactions necessary to mediate the matura- Heparitinase digestion tion of progenitors to the LPS-responsive stage are measured by Ig Cells were treated with heparitinase (from flavobacterium heparinum; secretion, the productive result of LPS-stimulation. These experi- Seikagaku/Associates of Cape Cod catalog no. 100703) at 0.1mU/ml/106 ments do not require IL-7, nor are they hindered by its presence. cells at 37°C for 60 min. Subsequently, cells were washed one time and Previous experiments (15) demonstrated that stromal cells could cultured in the presence of 0.02 mU heparitinase. An additional 0.02mU be replaced at this transition if IL-7-expanded B lineage cells were heparitinase was added every 24 h for the first 3 days of culture. This treatment was sufficient to reduce the epitope detected by the mAb cultured in conditions that promoted cell-cell contact (homotypic clone 10E4. interactions). Progenitors cultured in either condition become re- sponsive to LPS, which subsequently promotes further develop- FACS analysis ment and activation of the cells to secrete IgM. Although much of Cells were washed in FACS buffer (PBS, 3% FCS, and 0.01% sodium the current literature focuses on the interface between stromal cells azide) and resuspended in 96-well, round-bottom assay plates at 104-105 and preB cells, there is less known about potential mediators that cells in 15 ␮l. Labeling was done at 4°C for 15 min in a total volume of 65 ␮l containing optimized dilutions of the following Abs (clone): IgM promote development in the absence of stromal cells, such as in (33.60; made in-house), B220 (RA3-6B2; made in-house), CD2 (RM2-5; our system. For example, we have found that the addition of anti-␮ BD Biosciences), CD19 (MB19-1; eBioscience), CD43 (S7-5; BD Bio- Fab to these cultures prevented maturation (15). We could not sciences), CD117/c-kit (2B8; eBioscience), Ig␬ (187.1; BD Biosciences or detect signaling events initiated within the B cell progenitors ex- polyclonal goat anti-Ig␬; Southern Biotechnology), CD23 (clone B3B4; posed to the anti-␮ Fab and hypothesized that this reagent may BD Biosciences), IgD (10.4; made in-house), CD86 (M5/114; BD Bio- sciences), CD21 (7G6; BD Biosciences), CD22 (Cy34.1; BD Biosciences), block the interaction between the preBCR and an external ligand, BP1 (6C3; BD Biosciences), ␭5 (FS1; made in-house), HSA (M1/69; BD or it may disrupt the formation of oligomeric complexes of the Biosciences), CD5 (53-7; BD Biosciences), Mac1 (BD Biosciences), Downloaded from preBCR.
Load more

Recommended publications
  • 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]
  • Childhood Leukemia
    Onconurse.com Fact Sheet Childhood Leukemia The word leukemia literally means “white blood.” fungi. WBCs are produced and stored in the bone mar- Leukemia is the term used to describe cancer of the row and are released when needed by the body. If an blood-forming tissues known as bone marrow. This infection is present, the body produces extra WBCs. spongy material fills the long bones in the body and There are two main types of WBCs: produces blood cells. In leukemia, the bone marrow • Lymphocytes. There are two types that interact to factory creates an overabundance of diseased white prevent infection, fight viruses and fungi, and pro- cells that cannot perform their normal function of fight- vide immunity to disease: ing infection. As the bone marrow becomes packed with diseased white cells, production of red cells (which ° T cells attack infected cells, foreign tissue, carry oxygen and nutrients to body tissues) and and cancer cells. platelets (which help form clots to stop bleeding) slows B cells produce antibodies which destroy and stops. This results in a low red blood cell count ° foreign substances. (anemia) and a low platelet count (thrombocytopenia). • Granulocytes. There are four types that are the first Leukemia is a disease of the blood defense against infection: Blood is a vital liquid which supplies oxygen, food, hor- ° Monocytes are cells that contain enzymes that mones, and other necessary chemicals to all of the kill foreign bacteria. body’s cells. It also removes toxins and other waste products from the cells. Blood helps the lymph system ° Neutrophils are the most numerous WBCs to fight infection and carries the cells necessary for and are important in responding to foreign repairing injuries.
    [Show full text]
  • CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation
    CD48 Is Critically Involved in Allergic Eosinophilic Airway Inflammation Ariel Munitz,1 Ido Bachelet,1 Fred D. Finkelman,2 Marc E. Rothenberg,3 and Francesca Levi-Schaffer1,4 1Department of Pharmacology, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; 2Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; 3Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio; and 4David R. Bloom Center for Pharmacology, Hebrew University of Jerusalem, Jerusalem, Israel Rationale: Despite ongoing research, the molecular mechanisms con- trolling asthma are still elusive. CD48 is a glycosylphosphatidylinositol- AT A GLANCE COMMENTARY anchored protein involved in lymphocyte adhesion, activation, and costimulation. Although CD48 is widely expressed on hematopoi- Scientific Knowledge on the Subject etic cells and commonly studied in the context of natural killer and CD48 is an activation molecule able to facilitate various cytotoxic T cell functions, its role in helper T cell type 2 settings cellular activities. Its role in asthma is unknown. has not been examined. Objectives: To evaluate the expression and function of CD48, CD2, and 2B4 in a murine model of allergic eosinophilic airway inflammation. What This Study Adds to the Field Methods: Allergic eosinophilic airway inflammation was induced by CD48 is upregulated in experimental asthma. Anti-CD48– ovalbumin (OVA)–alum sensitization and intranasal inoculation of based therapies may be useful for asthma and perhaps OVA or, alternatively, by repeated intranasal inoculation of Aspergil- various allergic diseases. lus fumigatus antigen in wild-type, STAT (signal transducer and acti- vator of transcription)-6–deficient, and IL-4/IL-13–deficient BALB/c mice.
    [Show full text]
  • Supplementary Table 1: Adhesion Genes Data Set
    Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like,
    [Show full text]
  • A Novel Cytogenetic Aberration Found in Stem Cell Leukemia/Lymphoma Syndrome
    Letters to the Editor 644 normal PB buffy coat DNA (see example in Figure 1b). These marrow (used for MRD evaluation), the actual Quantitative data show that NSA can be variable, dependent on the type of Range for TCRG targets will often be underestimated. sample (bone marrow or peripheral blood) and the time point We conclude that the ESG-MRD-ALL guidelines for inter- during or after therapy. pretation of RQ-PCR data appropriately take into account the We next evaluated to what extent this variation in NSA variation in NSA. The guidelines for prevention of false-positive affected the RQ-PCR data interpretation, applying the guidelines MRD data perform well, with less than 2% false-positive results. for prevention of false-positive MRD results as well as the However, our data also clearly indicate that positive results guidelines for preventing false-negative MRD results. In Figures outside the Quantitative Range should always be judged with 2a-c, the data interpreted according to the guidelines for the caution, particularly for samples taken after cessation of therapy prevention of false-negative MRD results are shown. IGH targets and analyzed with Ig gene targets. Preferably, one should aim with NSA in normal PB buffy coat DNA resulted in false-positive for RQ-PCR assays without any NSA, since this will improve the MRD data in about 10% of samples obtained during therapy reliability of the data interpretation. (Figure 2a). However, in samples obtained after cessation of therapy (after week 104) false-positivity could be observed in up VHJ van der Velden, JM Wijkhuijs and JJM van Dongen Department of Immunology, Erasmus MC, University Medical to 65% of samples.
    [Show full text]
  • Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon
    www.nature.com/scientificreports OPEN Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Received: 17 November 2017 Accepted: 9 July 2018 Receptors Published: xx xx xxxx Jeremy P. McAleer1, Jun Fan2, Bryanna Roar1, Donald A. Primerano2 & James Denvir2 Th17 cells contribute to host defense on mucosal surfaces but also provoke autoimmune diseases when directed against self-antigens. Identifying therapeutic targets that regulate Th17 cell diferentiation and/or cytokine production has considerable value. Here, we study the aryl hydrocarbon receptor (AhR)- dependent transcriptome in human CD4 T cells treated with Th17-inducing cytokines. We show that the AhR reciprocally regulates IL-17 and IL-22 production in human CD4 T cells. Global gene expression analysis revealed that AhR ligation decreased IL21 expression, correlating with delayed upregulation of RORC during culture with Th17-inducing cytokines. Several of the AhR-dependent genes have known roles in cellular assembly, organization, development, growth and proliferation. We further show that expression of GPR15, GPR55 and GPR68 positively correlates with IL-22 production in the presence of the AhR agonist FICZ. Activation of GPR68 with the lorazepam derivative ogerin resulted in suppression of IL-22 and IL-10 secretion by T cells, with no efect on IL-17. Under neutral Th0 conditions, ogerin and the Gq/11 receptor inhibitor YM254890 blunted IL-22 induction by FICZ. These data reveal the AhR- dependent transcriptome in human CD4 T cells and suggest the mechanism through which the AhR regulates T cell function may be partially dependent on Gq-coupled receptors including GPR68.
    [Show full text]
  • Cell Surface Markers in Acute Lymphoblastic Leukemia* F
    ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 10, No. 3 Copyright © 1980, Institute for Clinical Science, Inc. Cell Surface Markers in Acute Lymphoblastic Leukemia* f G. BENNETT HUMPHREY, M.D., REBECCA BLACKSTOCK, Ph .D., AND JANICE FILLER, M.S. University of Oklahoma, Health Sciences Center, Oklahoma City, OK 73126 ABSTRACT During the last nine years, two important methodologies have been used to characterize the cell surfaces of normal lymphocytes and malignant lym­ phoblasts. Normal mature T-cells have a receptor for sheep erythrocytes (E+) while mature B-cells bear membrane-bound immunoglobulin molecules (slg+). These two findings can be used to divide acute lymphoblastic leukemia of childhood into three major groups; B-cell leukemia (slg+ E -), which is rare (approximately 2 percent) and has the poorest prognosis, T-cell leukemia (slg~, E +) which is more common (10 percent) but also has a poor prognosis and null cell leukemia (slg~, E~) which is the most common (85 percent) and has the best prognosis. By the use of additional immunological methods, subgroups within T-cell leukemia and null cell leukemia have also been proposed. One of the most valuable of these additional methods is the detection of surface antigens. Three of the more commonly detected antigens currently being evaluated are (1) common leukemia antigen (cALL), (2) a normal B Lymphocyte antigen the la antigen (la) which is not generally expressed on most T lympho­ cytes and (3) a normal T lymphocyte antigen (T) not expressed on B lympho­ cytes. Within null cell leukemia, the most commonly identified and proba­ bly the largest subgroup is Ia+, cALL+, T”, E _, slg-.
    [Show full text]
  • The Immunological Synapse and CD28-CD80 Interactions Shannon K
    © 2001 Nature Publishing Group http://immunol.nature.com ARTICLES The immunological synapse and CD28-CD80 interactions Shannon K. Bromley1,Andrea Iaboni2, Simon J. Davis2,Adrian Whitty3, Jonathan M. Green4, Andrey S. Shaw1,ArthurWeiss5 and Michael L. Dustin5,6 Published online: 19 November 2001, DOI: 10.1038/ni737 According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR–MHC-peptide recognition.The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR–MHC- peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28. The T cell receptor (TCR) interaction with complexes of peptide and as CD2 and CD48, which suggests that CD28 might have a dual role as major histocompatibility complex (pMHC) is central to the T cell an adhesion and a signaling molecule4. Coengagement of CD28 with response. However, efficient T cell activation also requires the partici- the TCR has a number of effects on T cell activation; these include pation of additional cell-surface receptors that engage nonpolymorphic increasing sensitivity to TCR stimulation and increasing the survival of ligands on antigen-presenting cells (APCs). Some of these molecules T cells after stimulation5. CD80-transfected APCs have been used to are involved in the “physical embrace” between T cells and APCs and assess the temporal relationship of TCR and CD28 signaling, as initiat- are characterized as adhesion molecules.
    [Show full text]
  • Proliferation by 2B4/CD48 Interactions T Cell
    Cutting Edge: Regulation of CD8+ T Cell Proliferation by 2B4/CD48 Interactions Taku Kambayashi, Erika Assarsson, Benedict J. Chambers and Hans-Gustaf Ljunggren This information is current as of September 29, 2021. J Immunol 2001; 167:6706-6710; ; doi: 10.4049/jimmunol.167.12.6706 http://www.jimmunol.org/content/167/12/6706 Downloaded from References This article cites 23 articles, 12 of which you can access for free at: http://www.jimmunol.org/content/167/12/6706.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 29, 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 © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. ● Cutting Edge: Regulation of CD8؉ T Cell Proliferation by 2B4/CD48 Interactions1 Taku Kambayashi,2* Erika Assarsson,2* Benedict J. Chambers,* and Hans-Gustaf Ljunggren3*† To date, the only known 2B4-binding molecule is CD48. Bind- The biological function of 2B4, a CD48-binding molecule ex- ing studies have shown that CD48 has a 5–10 times stronger af- pressed on T cells with an activation/memory phenotype, is not finity for 2B4 than for CD2 (7, 8).
    [Show full text]
  • Research Article Segmentation of White Blood Cell from Acute Lymphoblastic Leukemia Images Using Dual-Threshold Method
    Hindawi Publishing Corporation Computational and Mathematical Methods in Medicine Volume 2016, Article ID 9514707, 12 pages http://dx.doi.org/10.1155/2016/9514707 Research Article Segmentation of White Blood Cell from Acute Lymphoblastic Leukemia Images Using Dual-Threshold Method Yan Li,1,2 Rui Zhu,1 Lei Mi,1 Yihui Cao,1,2 and Di Yao3 1 State Key Laboratory of Transient Optics and Photonics, Xi’an Institute of Optics and Precision Mechanics of Chinese Academy of Sciences, Xi’an 710119, China 2University of Chinese Academy of Sciences, 52 Sanlihe Road, Beijing 100864, China 3Shenzhen Vivolight Medical Device and Technology Co., Ltd., Shenzhen 518000, China Correspondence should be addressed to Yan Li; [email protected] Received 30 December 2015; Revised 7 April 2016; Accepted 21 April 2016 Academic Editor: Jayaram K. Udupa Copyright © 2016 Yan Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We propose a dual-threshold method based on a strategic combination of RGB and HSV color space for white blood cell (WBC) segmentation. The proposed method consists of three main parts: preprocessing, threshold segmentation, and postprocessing. In the preprocessing part, we get two images for further processing: one contrast-stretched gray image and one H component image from transformed HSV color space. In the threshold segmentationpart,adual-thresholdmethodisproposedforimprovingthe conventional single-threshold approaches and a golden section search method is used for determining the optimal thresholds. For the postprocessing part, mathematical morphology and median filtering are utilized to denoise and remove incomplete WBCs.
    [Show full text]
  • A Hybrid Deep Learning Architecture for Leukemic B-Lymphoblast Classification
    A Hybrid Deep Learning Architecture for Leukemic B-lymphoblast Classification Sara Hosseinzadeh Kassani Peyman Hosseinzadeh Kassani Michal J. Wesolowski Department of Computer Science Department of Biomedical Engineering Department of Medical Imaging University of Saskatchewan University of Tulane University of Saskatchewan Saskatoon, Canada New Orleans, USA Saskatoon, Canada [email protected] [email protected] [email protected] Kevin A. Schneider Ralph Deters Department of Computer Science Department of Computer Science University of Saskatchewan University of Saskatchewan Saskatoon, Canada Saskatoon, Canada [email protected] [email protected] Abstract—Automatic detection of leukemic B-lymphoblast can- diagnosed and about 1500 patients are expected to die of ALL, cer in microscopic images is very challenging due to the com- including both children and adults, in the United States. The plicated nature of histopathological structures. To tackle this risk of getting ALL is slightly higher in males than females, issue, an automatic and robust diagnostic system is required for early detection and treatment. In this paper, an automated and higher in whites than African-Americans. However, if deep learning-based method is proposed to distinguish between leukemia is diagnosed in its early stages, it is highly curable immature leukemic blasts and normal cells. The proposed deep and increases the survival rate of the patients. Considering learning based hybrid method, which is enriched by different data the large-scale of histopathology images, assessment of the augmentation techniques, is able to extract high-level features images in a conventional way can be laborious, error-prone from input images. Results demonstrate that the proposed model yields better prediction than individual models for Leukemic B- and hugely time-consuming since some images are highly vari- lymphoblast classification with 96.17% overall accuracy, 95.17% able in morphology which is difficult to analyze.
    [Show full text]
  • Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age
    Cell Reports, Volume 25 Supplemental Information Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli Are Altered with Age Mati Mann, Arnav Mehta, Carl G. de Boer, Monika S. Kowalczyk, Kevin Lee, Pearce Haldeman, Noga Rogel, Abigail R. Knecht, Daneyal Farouq, Aviv Regev, and David Baltimore A B 80 Young 60 Young Aged Aged *** *** 60 40 * * 40 *** *** * *** *** * 20 20 0 0 Myeloid cells (% of CD45+ cells) Granulocytes (% of CD45+ cells) C Young D Young 40 Aged 80 Aged *** 30 *** 60 *** *** *** *** *** 20 40 10 20 T cells (% of CD45+ cells) B cells (% of CD45+ cells) 0 0 0 hr 72 hr 3 wk 6 wk 9 wk 0 hr 72 hr 3 wk 6 wk 9 wk E Spleen F Bone marrow 30 ** 1.5 * 0.3 * ) ) CD45 f ) 1.0 0.2 20 Lin- o f Lin- o (% f s (% o ell (% Cs c 0.5 S 0.1 10 -H SKs eloid L LT My 0 0.0 0.0 35 *** 0.20 * 0.8 NS ) ) 0.15 ) 0.6 Lin- 30 Lin- f f CD45 o o f o (% 0.10 (% 0.4 s (% s SC PPs ell M 25 -H T c ST 0.05 0.2 20 0 0 Young Aged Young Aged Young Aged Figure S1. Aged mice challenged with LPS demonstrate increased myeloid output and an increased frequency of bone marrow HSPCs. Related to Figure 1. (A)-(C) Young (8-12 weeks) and aged (20-24 months) mice were exposed to single sub-lethal dose of LPS and peripheral blood (A) myeloid cell and (B) granulocyte (C) T cell, (D) B cell, frequencies were measured by flow cytometry at the indicated time points after LPS exposure (n = 4-14 per group).
    [Show full text]