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 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.
CBR Institute for Biomedical Research, Department of Pathology, Harvard Medical School, Boston, MA, USA.
Jean-Marc
JM
Gauguet
Steven D
SD
Rosen
Jamey D
JD
Marth
Ulrich H
UH
von Andrian
D000818:Animals; D004730:Endothelium, Vascular / Q000201:enzymology*; D019041:L-Selectin / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology*; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017351:N-Acetylglucosaminyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014699:Venules; D000097811:Carbohydrate Sulfotransferases
D019041:L-Selectin; D017351:N-Acetylglucosaminyltransferases; D016201:Receptors, Lymphocyte Homing; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C106501:N-acetylglucosaminyltransferase IGnT