CD48 DELIVERS AN ACCESSORY SIGNAL FOR CD40-MEDIATED ACTIVATION OF HUMAN B-CELLS

CD48, a glycosyl phosphatidylinositol anchored molecule has recently b een shown to be a ligand for the T cell surface protein CD2 in mouse, human, and rat. It is expressed on practically all human T and B cells ; however, its function remains unknown. We examined whether CD48 may be involved in the delivery of activating signals to human B cells. Co stimulation with anti-CD48 J4-57 significantly increased CD40-mediated activation of tonsillar B cells. Costimulatory effect of anti-CD48 wa s observed on B cell aggregation, proliferation, and IgG secretion, An ti-CD48 alone did not stimulate resting B cells. Accessory signal prov ided through CD48 required the presence of IL-4 and/or IL-10, whereas responses of B cells to IL-2 was not affected. Ligation of CD48 by spe cific antibody induced CD23 expression on IL-4-stimulated Ramos B cell line but did not affect expression of CD25, We also examined the bioc hemical nature of the costimulatory effect of anti-CD40 and CD48. Liga tion of CD40 or CD48 on the B cells induced tyrosine phosphorylation o f proteins. CD40 induced earlier changes in the protein phosphorylatio n than CD48 did, Taken together, our data suggest that the stimulation via CD40 provides initial signals to activate B cells and CD48 may be involved in enhancing the activating signal to B cells, resulting in increased responsiveness of B cells to IL-4 and IL-10. (C) 1996 Academ ic Press, Inc.