Detection of a Sulfotransferase (HEC-GlcNAc6ST) in High Endothelial Venules of Lymph Nodes and in High Endothelial Venule-Like Vessels within Ectopic Lymphoid Aggregates: Relationship to the MECA-79 Epitope

• Published in: The American journal of pathology Vol. 164; no. 5; pp. 1635 - 1644
• Main Authors: Bistrup, Annette, Tsay, Durwin, Shenoy, Priti, Singer, Mark S, Bangia, Naveen, Luther, Sanjiv A, Cyster, Jason G, Ruddle, Nancy H, Rosen, Steven D
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.05.2004; American Society for Investigative Pathology
• Subjects: Animals; Antigens, Surface - chemistry; Antigens, Surface - metabolism; Biological and medical sciences; Blotting, Western; Carbohydrate Sulfotransferases; Cell Adhesion Molecules; DNA, Complementary - metabolism; Endothelium - enzymology; Enzyme-Linked Immunosorbent Assay; Epitopes - chemistry; General aspects; Ligands; Lymph Nodes - enzymology; Lymph Nodes - pathology; Lymphocytes - enzymology; Medical sciences; Membrane Proteins; Mice; Microscopy, Fluorescence; Mucoproteins; Regular; Sulfotransferases - biosynthesis; High; Sulfotransferases; Antigenic determinant; Lymph node; Enzyme; Transferases; Venule; Endothelium; Medicine; Microcirculation; Circulatory system; Ectopia; Detection
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63722-4

The interaction of L-selectin on lymphocytes with sulfated ligands on high endothelial venules (HEVs) of lymph nodes results in lymphocyte rolling and is essential for lymphocyte homing. The MECA-79 monoclonal antibody reports HEV-expressed ligands for L-selectin by recognizing a critical sulfation-dependent determinant on these ligands. HEC-GlcNAc6ST, a HEV-localized sulfotransferase, is essential for the elaboration of functional ligands within lymph nodes, as well as the generation of the MECA-79 epitope. Here, we use an antibody against murine HEC-GlcNAc6ST to study its expression in relationship to the MECA-79 epitope. In lymph nodes, the enzyme is expressed in the Golgi apparatus of high endothelial cells, in close correspondence with luminal staining by MECA-79. In lymph node HEVs of HEC-GlcNAc6ST-null mice, luminal staining by MECA-79 is almost abolished, whereas abluminal staining persists although reduced in intensity. HEV-like vessels in several examples of inflammation-associated lymphoid neogenesis, including nonobese diabetic mice, also exhibit concomitant expression of the sulfotransferase and luminal MECA-79 reactivity. The correlation extends to ectopic lymphoid aggregates within the pancreas of RIP-BLC mice, in which CXCL13 is expressed in islets. Analysis of the progeny of RIP-BLC by HEC-GlcNAc6ST-null mice establishes that the enzyme is responsible for the MECA-79 defined luminal ligands.