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Memory B lymphocytes from secondary lymphoid organs interact with E- selectin through a novel glycoprotein ligand

Abstract:

Recirculation of B lymphocytes through the secondary lymphoid organs is key for recognition and response to foreign antigen. B lymphocytes within secondary lymphoid organs comprise a heterogeneous population of cells at distinct differentiation stages. To ascribe a particular adhesive behavior to discrete B-cell subsets within secondary lymphoid organs, we investigated their functional interaction with endothelial selectins under flow. We describe herein the characterization of a subset of human tonsillar B cells that interact with E-selectin but not P-selectin. E-selectin-interacting B cells had a phenotype of non-germinal center (CD10-, CD38-, CD44+), memory (IgD-) cells. Furthermore, FucT-VII was expressed selectively in CD44+ E- selectin-adherent B lymphocytes. B-cell rolling on E-selectin required sialic acid but was independent of previously described selectin ligands. A novel glycoprotein ligand of 240 kDa carrying N-linked glycans was isolated from B- cell membranes by an E-selectin immunoadhesin. Binding of this protein was strictly Ca2+ dependent, was inhibited by a cell adhesion-blocking mAb 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 roiling on E-selectin, that provides insights on the adhesion pathways involved in homing of memory B cells to tertiary sites.