Early events in Epstein-Barr virus infection provide a model for B cell activation.

Abstract

Epstein-Barr virus (EBV) infection was used in vitro to delineate 2 distinct stages in human B cell activation. Previously, the BLAST-2 (EBVCS) (EBV cell surface) activation antigen was shown to be expressed on a small fraction of B cells within 24 h of stimulation with a variety of agents, including mitogens and EBV. Here, the BLAST-2 (EBVCS)+ cells were isolated early after activation/infection with EBV. These cells are small B cells that are actively synthesizing RNA but not DNA, and are, therefore, clearly distinct from large proliferating lymphoblasts. In addition, they contain multiple copies of the EBV genome, express the viral nuclear antigen (EBNA) and proceed to undergo transformation when placed back in culture. The BLAST-2 (EBVCS)- population does not undergo transformation, even though a fraction of these cells are activated for RNA synthesis and express EBNA. Thus, using the EBV system, it was shown directly than an activated B cell first expresses the BLAST-2 (EBVCS) antigen concomitant with an increase in RNA synthesis, and then subsequently proceeds to differentiate into a proliferating lymphoblast.