Inhibition of cell growth and Epstein-Barr virus reactivation by CD40 stimulation in Epstein-Barr virus-transformed B cells

The CD40 molecule plays important roles in B cell activation, proliferation , and immunoglobulin (Ig) class switching, In Epstein-Barr virus (EBV)-tran sformed lymphoblastoid cell lines (LCL), CD40 mediates growth inhibition an d EBV reactivation via the CD40 signaling pathways. CD40 cross-linking with a monoclonal antibody arrests cell growth in G(1) and induces expression o f p27(kip1) cyclin-dependent kinase inhibitor. CD40 cross-linking also indu ces EBV reactivation, as detected by the induction of EBV-specific early an tigen, immediate early BZLF1 RNA, and its protein product ZEBRA, These resu lts support hypotheses that the proliferation of EBV-infected B cells in vi vo can be inhibited by interactions with the CD40 ligand on activated helpe r T cells, and latent EBV is reactivated via the signaling pathways control led by CD40 interactions.