EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway

Department of Microbiology and Immunology, Northwestern University, Chicago, IL 60611, USA Correspondence Richard Longnecker r-longnecker{at}northwestern.edu Latent membrane protein 2A (LMP2A) of Epstein–Barr virus (EBV) provides developmental and survival signals that mimic those of a B-cell receptor (BCR). Expression of LMP2A during B-cell development results in the ability of B cells to exit the bone marrow in the absence of a BCR and persist in the periphery, where they would normally undergo apoptosis. This study extends the current knowledge of LMP2A function by examining the growth properties of bone marrow B cells from TgE LMP2A mice. Despite the lack of pre-BCR expression, bone marrow B cells from TgE LMP2A mice proliferate and survive in low concentrations of interleukin 7, similar to wild-type cells. Constitutive phosphorylation of ERK/MAPK and PI3K/Akt in TgE LMP2A bone marrow B cells is also reminiscent of signalling through the pre-BCR, altogether demonstrating that LMP2A provides a pre-BCR-like signal to developing B cells. Published online ahead of print on as DOI 10.1099/vir.0.2008/001461-0.