Siglec-7 tetramers characterize B-cell subpopulations and leukemic blasts

European Journal of Immunology
Friederike GiesekeIngo Müller

Abstract

Cell surface glycosylation has important regulatory functions in the maturation, activation, and homeostasis of lymphocytes. The family of human sialic acid-binding immunoglobulin-like lectins (siglecs) comprises inhibitory as well as activating receptors intimately involved in the regulation of immune responses. Analyses of the interaction between siglecs and glycans are hampered by the low affinity of this interaction. Therefore, we expressed siglec-7 in eukaryotic cells, allowing for glycosylation, and oligomerized the protein in analogy to MHC tetramers. Using this tool, flow cytometric analysis of lymphocytes became possible. Sialic acid-dependent binding of siglec-7 tetramers was confirmed by glycan array analysis and loss of siglec tetramer binding after neuraminidase treatment of lymphocytes. In contrast to most lymphocyte subpopulations, which showed high siglec-7 ligand expression, B-cell subpopulations could be further subdivided according to different siglec-7 ligand expression levels. We also analyzed blasts from acute lymphoblastic leukemias of the B-cell lineage as well as the T-cell lineage, since malignant transformation is often associated with aberrant cell surface glycosylation. While pediatric T-ALL blasts ...Continue Reading

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Citations

Feb 27, 2014·The Journal of Clinical Investigation·Camilla JandusStephan von Gunten
Jan 28, 2015·Protein Expression and Purification·Johannes M PröpsterMario Schubert
Oct 11, 2020·Nature Communications·Emily RodriguesMatthew S Macauley
Jan 27, 2021·Proceedings of the National Academy of Sciences of the United States of America·Simon WisnovskyCarolyn R Bertozzi

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