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bioRxiv · 10.1101/604264

B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism

Irons, E. E.·Lee-Sundlov, M. M.·Hoffmeister, K. M.·Lau, J. T. Y.
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Abstract

The immune response relies on the timely integration of cell-intrinsic processes with cell-extrinsic cues. During infection, B cells vacate the bone marrow for the emergency generation of granulocytes. However, it is unclear if cross-talk between B cells and neutrophils also encourages the return to homeostasis. Here, we report that B cells remodel glycans on hematopoietic progenitors to suppress granulopoiesis. Human B cells secrete active ST6Gal-1 sialyltransferase to modify the sialylation and Gr-1 expression of co-cultured hematopoietic progenitors. After adoptive transfer, total hematopoietic and B cells modified the sialylation of non-self cells and elevated blood ST6Gal-1. Mature IgD+ B cells co-localized with megakaryocytes to sialylated bone marrow niches, suggesting their role in medullary extrinsic sialylation. Finally, ST6Gal-1 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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Irons, E. E., Lee-Sundlov, M. M., Hoffmeister, K. M., Lau, J. T. Y.. 2019-04-09. B cells suppress medullary granulopoiesis by an extracellular glycosylation-dependent mechanism. https://doi.org/10.1101/604264

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