The scavenger receptor (SR-A) is considered to play a role in host defense by scavenging endotoxins, oxidized proteins, and denatured or otherwise modified self components, which are routed toward degradation in macrophages. Recent data suggest that SR-A also functions as an adhesion molecule. Our previous finding of SR-A expression by high endothelial cells of venules and on follicular dendritic cells in peripheral lymph nodes prompted us to investigate whether SR-A can act as an addressin for lymphocytes. We describe here that activated B cells adhere to CHO cells transfected with either the type I or type II isoform of SR-A. In contrast, resting B cells isolated from peripheral blood did not adhere to SR-A transfected CHO cells. Other types of leukocytes did not bind to SR-A. The adhesive properties of B lymphocytes in different stages of activation were further explored using lymphoma cell lines of the B cell lineage. The in vitro EBV-transformed B cell line IARC171 showed enhanced adhesiveness to SR-A, whereas the Burkitt lymphoma cell lines, BL41, Rael, and Bl16 did not. The SR-A-dependent adhesion of B-lymphoblasts occurred both at 37 and 4 degrees C, suggesting that it was not dependent on cell metabolism. The known polyanionic ligands for SR-A, fucoidan, and acetylated low density lipoprotein, which bind to a positively charged portion of the collagen-like domain of SR-A, did not inhibit adhesion. This finding suggests that SR-A mediates adhesion of activated B lymphocytes through a binding site that differs from the one that binds polyanionic ligands. Together, our data suggest that SR-A plays a role in the recruitment of activated B cells into lymph nodes and inflammatory lesions by acting as an adhesion molecule for such cells.