B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism
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.
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All data generated or analyzed in this study are included in the manuscript and supporting files.
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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.
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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