B cells sialylate bone marrow progenitors to inhibit granulocyte production

Abstract

Abstract Effective hematopoiesis is predicated on the utilization of limited resources and space in the bone marrow during homeostasis and stress. During acute inflammation, secreted factors induce the egress of mature B cells from the medullary compartment, reclaiming space for the emergency proliferation of myeloid precursors. However, it remains unclear whether reciprocal mechanisms between B cells and myeloid cells exist during homeostasis. Recent work by our group has demonstrated the ability of extracellular glycosyltransferases to remodel plasma membrane glycans, altering cell sensitivity to growth factors. Here, we report that B cells secrete active ST6GAL1 sialyltransferase, capable of glycosylating cells by a non-cell autonomous, extrinsic mechanism. B cells secreted ST6GAL1 to glycosylate hematopoietic progenitors in co-culture, suppressing G-CSF-driven neutrophil production. In vivo, B cell-derived ST6GAL1 restored circulating enzyme levels and altered the sialylation of diverse hematopoietic populations after transplantation into St6gal1-deficient mice. In the bone marrow, colonizing IgD+ mature B cells colocalized with regions rich in sialylation. Finally, in the bone marrow of multiple myeloma patients, expression of ST6GAL1 correlated negatively with neutrophil abundance. Our findings underscore a novel mechanism of cross-talk between mature lymphocytes and myeloid progenitors involving paracrine extracellular sialylation, with potential implications for human disease.