1. Immunology and Inflammation
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B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism

  1. Eric E Irons
  2. Melissa M Lee-Sundlov
  3. Yuqi Zhu
  4. Sriram Neelamegham
  5. Karin M Hoffmeister
  6. Joseph TY Lau  Is a corresponding author
  1. Roswell Park Comprehensive Cancer Center, United States
  2. Blood Research Institute Versiti, United States
  3. University at Buffalo, United States
Research Article
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Cite this article as: eLife 2019;8:e47328 doi: 10.7554/eLife.47328

Abstract

The immune response relies on the integration of cell-intrinsic processes with cell-extrinsic cues. During infection, B cells vacate the marrow for emergency granulopoiesis. However, it is unclear if cross-talk between B cells and neutrophils also encourages B cell return to homeostasis. Here, we report that B cells remodel glycans on hematopoietic progenitors to suppress granulopoiesis. Human B cells secrete active ST6GAL1 sialyltransferase to modify the sialylation and Gr-1 expression of co-cultured with mouse hematopoietic progenitors. In mouse models, ST6GAL1 from B cells can alter the sialylation of bone marrow populations. Mature IgD+ B cells were enriched in sialylated bone marrow niches, suggesting a role in medullary extrinsic sialylation. Finally, ST6GAL1 expression in multiple myeloma cells negatively correlated with neutrophil abundance in human patients. Our results highlight the growing significance of extracellular glycoslytransferases as mediators of a novel glycan-dependent interaction between B cells and granulocytes.

Article and author information

Author details

  1. Eric E Irons

    Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Melissa M Lee-Sundlov

    Translational Glycomics Center, Blood Research Institute Versiti, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8290-8586
  3. Yuqi Zhu

    Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sriram Neelamegham

    Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Karin M Hoffmeister

    Transfusion Medicine, Blood Research Institute Versiti, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Joseph TY Lau

    Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, United States
    For correspondence
    joseph.lau@roswellpark.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5128-2664

Funding

National Institutes of Health (R01AI140736)

  • Joseph TY Lau

National Institutes of Health (R01HL089224)

  • Karin M Hoffmeister

National Institutes of Health (K12HL141954)

  • Joseph TY Lau

National Institutes of Health (K12HK141954)

  • Karin M Hoffmeister

National Cancer Institute (CA076056)

  • Joseph TY Lau

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Roswell Park Institute of Animal Care and Use Committee approved maintenance of animals and all procedures used, under protocol 1071M.

Reviewing Editor

  1. Jamey Marth, University of California, Santa Barbara, United States

Publication history

  1. Received: April 2, 2019
  2. Accepted: August 10, 2019
  3. Accepted Manuscript published: August 13, 2019 (version 1)

Copyright

© 2019, Irons et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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