| |
|
|
|
|
|
|
|||
|
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.
Submitted May 28, 2004
Department of Pathology, CBR Institute for Biomedical Research, Inc., Harvard Medical School, Boston, MA, 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.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright © 2004 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||