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

Recirculation of B lymphocytes through the secondary lymphoid organs is key for recognition and response to foreign antigen. B lymphocytes within seco ndary lymphoid organs comprise a heterogeneous population of cells at disti nct differentiation stages. To ascribe a particular adhesive behavior to di screte B-cell subsets within secondary lymphoid organs, we investigated the ir functional interaction with endothelial selectins under flow. We describ e herein the characterization of a subset of human tonsillar B cells that i nteract with E-selectin but not P-selectin. E-selectin-interacting B cells had a phenotype of non-germinal center (CD 10(-), 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 s ialic 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 prot ein 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 rolling on E-selectin, that prov ides insights on the adhesion pathways involved in homing of memory B cells to tertiary sites.