Induction of aggregation in porcine lymphoid cells by antibodies to CD46

CD46 is a major transmembrane glycoprotein that belongs to the regulator of complement activation (RCA) family. Recently, mAbs to human CD46 were show n to suppress IL-12 production. Here, we describe that mAbs against differe nt porcine CD46 epitopes induced a marked adhesion of normal lymphocytes. A ddition of low amounts of antibody to freshly isolated lymphocytes or thymo cytes resulted in the clustering of the cells. Cross-linking of CD46 molecu les seems essential since Fab fragments failed to induce aggregation. This aggregation was dependent on active cell metabolism and on the presence of divalent cations and required a functional cytoskeleton. It was not inhibit ed by antibodies to CD18, CD29, CD2, CD11a and CD11b. Staurosporine, an inh ibitor of protein kinases, partially blocked the aggregation. This finding is indicative of a role of protein kinases in the transduction of the signa l generated by CD46 engagement. (C) 2000 Elsevier Science B.V. All rights r eserved.