Core 2 branching beta1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes

Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslation...

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Bibliographic Details
Published in:Blood 2004-12, Vol.104 (13), p.4104-4112
Main Authors: Gauguet, Jean-Marc, Rosen, Steven D, Marth, Jamey D, von Andrian, Ulrich H
Format: Article
Language:English
Subjects:
Animals
Carbohydrate Sulfotransferases
Endothelium, Vascular - enzymology
L-Selectin - physiology
Lymph Nodes - immunology
Lymphocyte Count
Mice
Mice, Inbred C57BL
Mice, Knockout
N-Acetylglucosaminyltransferases - deficiency
N-Acetylglucosaminyltransferases - genetics
N-Acetylglucosaminyltransferases - metabolism
Receptors, Lymphocyte Homing - immunology
Sulfotransferases - deficiency
Sulfotransferases - genetics
Sulfotransferases - metabolism
T-Lymphocytes - immunology
Venules
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Summary:Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I(-/-) and HEC-GlcNAc6ST(-/-) mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (V(roll)) in C2GlcNAcT-I(-/-) mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST(-/-) HEVs, but V(roll) was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin(+/-) T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing.
ISSN:0006-4971