Resembled responses initiated by an activated BCR. The role of LMP2A in proliferation and transformation is less clear, with some studies claiming the protein plays no role in proliferation and transformation of B cells in vitro, while other studies have demonstrated an essential role in this process. Interestingly, LMP2A expression in HaCaT epithelial cells induces morphological changes that coincide with increased proliferation and loss of differentiation markers and cell anchorage, demonstrating that LMP2A signaling induces epithelial cell transformation. LMP2B exon 1 is noncoding, and, therefore, LMP2B lacks an N-terminal signaling domain. Transcription of LMP2B initiates at a bidirectional promoter that is shared with LMP1, a protein that is critical for B cell transformation in vitro. The LMP2A and LMP2B transcripts are identical in exons 2�C9, which encodes the 12 TMs and a C-terminal tail that is required for protein aggregation. Without a signaling domain, LMP2B by itself cannot initiate a BCR-like signal, but it localizes to intracellular regions in B cells that contain signaling proteins, such as LMP2A and CD19. Although no role has as yet been demonstrated for LMP2B in either the activation or proliferation of B cells, many EBVrelated malignancies, such as HL, NPC and gastric carcinoma, express both LMP2 isoforms. Previous studies suggest that LMP2A and LMP2B contribute to epithelial cell spreading and motility, and may contribute to epithelial cell transformation. LMP2B has been implicated as a critical player in the switch from viral latency to lytic reactivation. In this work, we present an analysis of the 
role of the EBV proteins LMP2A and LMP2B in early B cell infection in vitro. Our analysis was performed using viruses deficient in LMP2A and/or LMP2B for infection of human B cells obtained from healthy donors in order to assess the roles of these proteins in the processes of activation, proliferation, and survival during early infection. In addition, we examined roles for LMP2A and LMP2B as regulators of latent gene expression and viral latency that could further explain differences in early infection kinetics. Infection of human B cells with LMP2A KO viruses led to a Albaspidin-AA marked decrease in activation and proliferation, as well as higher levels of apoptosis, which led to inefficient long-term growth of the infected B cells in culture. LMP2B did not play a significant role in B cell activation, proliferation, or survival in early infection, nor was it necessary for long-term growth of infected B cells. The loss of LMP2A and LMP2B expression did not significantly affect latent gene expression, with the exception of LMP2B transcript in D2Ainfected cells, nor did these genes appear to regulate latency and lytic induction in early infection. Our results suggest that LMP2A augments activation, proliferation and survival of B cells following EBV infection, which affects the ability of EBV to provide infected cells with an environment conducive to long-term outgrowth. In contrast, LMP2B does not significantly affect B cell activation, nor does this protein play a major role in proliferation and survival during early infection, as long-term outgrowth occurs similarly to wt. In this study, we have demonstrated that expression of LMP2A augments early activation and proliferation of EBV-infected B cells. This appears to be critical for 4-(Benzyloxy)phenol subsequent establishment of LCLs, since loss of LMP2A expression correlates with reduced LCL formation. Previous studies demonstrated the dispensability of LMP2A for establishment of LCLs.