IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms2334.html
   My bibliography  Save this article

Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation

Author

Listed:
  • Isabel Romero-Camarero

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Xiaoyu Jiang

    (University of Miami, Sylvester Comprehensive Cancer Center)

  • Yasodha Natkunam

    (Stanford University School of Medicine)

  • Xiaoqing Lu

    (University of Miami, Sylvester Comprehensive Cancer Center)

  • Carolina Vicente-Dueñas

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Ines Gonzalez-Herrero

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Teresa Flores

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Juan Luis Garcia

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • George McNamara

    (Analytical Imaging Core Facility (AICF), University of Miami)

  • Christian Kunder

    (Stanford University School of Medicine)

  • Shuchun Zhao

    (Stanford University School of Medicine)

  • Victor Segura

    (Center for Applied Medical Research (CIMA), University of Navarra)

  • Lorena Fontan

    (Center for Applied Medical Research (CIMA), University of Navarra)

  • Jose A. Martínez-Climent

    (Center for Applied Medical Research (CIMA), University of Navarra)

  • Francisco Javier García-Criado

    (University of Salamanca)

  • Jason D. Theis

    (Mayo Clinic)

  • Ahmet Dogan

    (Mayo Clinic)

  • Elena Campos-Sánchez

    (Centro de Biologia Molecular Severo Ochoa, CSIC/Universidad Autonoma)

  • Michael R. Green

    (Stanford University School of Medicine)

  • Ash A. Alizadeh

    (Stanford University School of Medicine)

  • Cesar Cobaleda

    (Centro de Biologia Molecular Severo Ochoa, CSIC/Universidad Autonoma)

  • Isidro Sánchez-García

    (Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca
    Institute of Biomedical Research of Salamanca (IBSAL))

  • Izidore S Lossos

    (University of Miami, Sylvester Comprehensive Cancer Center
    University of Miami)

Abstract

The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.

Suggested Citation

  • Isabel Romero-Camarero & Xiaoyu Jiang & Yasodha Natkunam & Xiaoqing Lu & Carolina Vicente-Dueñas & Ines Gonzalez-Herrero & Teresa Flores & Juan Luis Garcia & George McNamara & Christian Kunder & Shuch, 2013. "Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2334
    DOI: 10.1038/ncomms2334
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms2334
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms2334?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2334. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.