Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses

The effect of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) on the activation and differentiation of normal B cells was investigated. B cells of transgenic mice expressing LMP1 under the control of immunoglobu lin promoter/enhancer displayed enhanced expression of activation antigens and spontaneously proliferated and produced antibody. Humoral immune respon ses of LMP1 transgenic mice in CD40-deficient or normal backgrounds reveale d that LMP1 mimics CD40 signals to induce extrafollicular 13 cell different iation but, unlike CD40, blocks germinal center formation. Thus, these spec ific properties of LMP1 may determine the site of primary B cell infection and the state of infection in the natural course of EBV infection, whereas subsequent loss of LMP1 expression may affect the site of persistent latent infection.