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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4104-4112. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-05-1986. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-05-1986v1 104/13/4104    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gauguet, J.-M. Articles by von Andrian, U. H Search for Related Content PubMed PubMed Citation Articles by Gauguet, J.-M. Articles by von Andrian, U. H Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 28, 2004 Accepted August 2, 2004 Core 2 branching 1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B and T lymphocyte homing to peripheral lymph nodes Jean-Marc Gauguet, Steven D Rosen, Jamey D Marth, and Ulrich H von Andrian* Department of Pathology, CBR Institute for Biomedical Research, Inc., Harvard Medical School, Boston, MA, USA Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California, San Francisco, CA, USA Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, San Diego, CA, USA * Corresponding author; email: uva{at}cbr.med.harvard.edu. Blood borne lymphocyte trafficking to peripheral lymph nodes (PLN) depends upon successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEV). Biochemical analysis of purified L-selectin ligands has identified post-translational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HEC-GlcNAc6ST). Consequently, lymphocyte migration to PLN 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 HEV revealed a defect in B cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than for T cells. By contrast, B and T cell tethering was normal in HEC-GlcNAc6ST-/- HEV, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was due to their lower expression levels of L-selectin since L-selectin+/- T cells expressing equivalent L-selectin levels as B cells, exhibited similar intravascular behavior as 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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