A novel glycoprotein ligand of 240 kDa carrying N-linked glycans was isolated from B-cell membranes by an E-selectin immunoadhesin. against E-selectin, and required the presence of sialic acid but not N-linked carbohydrates. Our results enable us to assign to resident memory B lymphocytes a novel adhesion function, the rolling on E-selectin, that provides insights on the adhesion pathways involved in homing of memory B cells to tertiary sites. Introduction B lymphocytes continuously recirculate through the blood and secondary lymphoid organs, such as peripheral lymph nodes, spleen, Peyers patches, or tonsils, thus allowing them to encounter and react to antigen localized at these sites. Naive B cells enter the tonsils and will either continue the recirculation surveillance process in case they do not encounter antigen, or they will specifically recognize and respond to antigen located in the tonsils. B cells that encounter antigen become activated and undergo clonal expansion and somatic hypermutation that leads to differentiation into memory and plasma cells (1, 2). These cells return to the circulation, and some are directed to tertiary sites where they will exert their effector functions (3). B cells within secondary lymphoid organs can thus be classified, depending on their differentiation stage, into discrete subpopulations that are located at different compartments within these organs. B-cell subpopulations, including naive, germinal center (GC), memory, KRN2 bromide or plasma cells, KRN2 bromide can be phenotypically characterized by their differential expression of several cell surface markers (1). The selectin family of adhesion molecules has been classically implicated in the initial steps of the interaction of lymphocytes with the endothelium during lymphocyte homing. L-selectin, expressed by most circulating lymphocytes, is the principal receptor implicated in the interaction of lymphocytes with high endothelial venules (HEV), which may be the initial step because of their entry into supplementary lymphoid organs. This molecule also mediates lymphocyte recruitment to inflammatory sites (4). P-selectin, portrayed by platelets and endothelial cells after activation with inflammatory mediators quickly, continues to be implicated in early leukocyte moving through the inflammatory response (4). E-selectin can be an inducible endothelial adhesion molecule also, although its appearance comes after slower kinetics, achieving its optimum level after 4C6 hours of arousal with inflammatory mediators. This molecule is normally involved with leukocyte moving during chronic and severe irritation (5, 6). Moreover, E-selectin continues to be within endothelium going through pipe and proliferation development, implicating this molecule in angiogenesis (7 hence, 8). Hence, the function of E-selectin isn’t limited to mediating leukocyte-endothelial connections during inflammation. Appropriately, constitutive appearance of E-selectin continues to be reported at low amounts in venules of tonsils, adenoids, epidermis, and hematopoietic tissue (9C13). Furthermore, appearance of E-selectin continues to be NF-ATC reported on the top of astrocytes and hepatocytes (14, 15). Carbohydrate buildings, such as for example Lex, sLex, or Lea, decorate glycoproteins which have been defined as the high-affinity selectin ligands. Appearance of useful selectin ligands needs the actions of (1-3)-fucosyltransferases (FucTs). A number of these enzymes have already been described, although just FucT-IV and -VII have already been mixed up in synthesis of E-selectin ligands in leukocytes (4). Mucin-like glycoprotein ligands of selectins had been discovered by affinity isolation using antibody-like selectin fusion protein. P-selectin glycoprotein ligand-1 (PSGL-1) was initially defined as a P-selectin ligand (16, 17), though it in addition has been reported to bind KRN2 bromide E-selectin (16, 18) and L-selectin (19C21). KRN2 bromide This molecule mediates moving on P-selectin (19C22), nonetheless it struggles to mediate moving on E-selectin on specific cell types (22, 23). Furthermore, L-selectin has been proposed being a high-affinity ligand for E-selectin (24, 25)..
