CR2 and non-Hodgkin lymphoma: Not only can it promote HCV cellular entry by binding to CD81 on B-cell surface but when E2 binds to B cells via CD81, this latter then associates with CD19 and CD21, forming a complex that lowers the activation threshold.40 The synergy between CD81-CD19-CD21 complex signaling and BCR cross-activation by envelope glycoprotein E2 and/or NS3 is thought to promote B-cell proliferation, emergence of autoreactive clones, genomic instability and NHL development.