CD54 INTERCELLULAR ADHESION MOLECULE-1 AND MAJOR HISTOCOMPATIBILITY COMPLEX-II SIGNALING INDUCES B-CELLS TO EXPRESS INTERLEUKIN-2 RECEPTORSAND COMPLEMENTS HELP PROVIDED THROUGH CD40 LIGATION/

We have examined signaling roles for CD54 intercellular adhesion molec ule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-depen dent helper system that was previously shown to be contact as well as interleukin 2 (IL-2) dependent to demonstrate the relative roles of CD 54, MHC II, and CD40 signaling in the events leading to the induction of B cell proliferation and responsiveness to IL-2. Paraformaldehyde-f ixed activated Th1-induced expression of IL-2R alpha, IL-2R beta, and B7, and upregulated MHC II and CD54 on B cells. Anti-CD54 and MHC II m Abs as well as a CD8 alpha-CD40 ligand (L) soluble construct inhibited both the T-dependent induction of Ig secretion, and B cell phenotypic changes. We then compared the effects of activated Th1 cells with tha t of cross-linking these molecules. Cross-linking of CD54 and MHC II r esulted in the upregulated expression of MHC II and of CD54 and B7, re spectively, analogous to the effect of fixed activated Th1 cells. B7 e xpression was further enhanced by co-cross-linking CD54 and MHC II. Cr osslinking of CD40 achieved comparable effects. Strikingly, cross-link ing ligation of CD54 and MHC II in the presence of IL-5 induced expres sion of a functional IL-2R on small resting B cells. By contrast CD40 ligation, which induced B cell proliferation, did not induce IL-2 resp onsiveness. These data show that CD40 ligation is necessary but may no t be sufficient for B cell differentiation and identify CD54 and MHC I I as contact ligands that can complement CD40 signaling in the generat ion of T-dependent B cell responses to IL-2.