EBV utilizes a unique activation pathway for the transformation of human B cells

Abstract

EBV growth-transforms primate B lymphocytes and directly causes mono/mutticional B cell lymphomas In vulnerable hosts. In this report we demonstrate that the degree of B cell transformability Is not quantitatively determined at the level of either the saturable, transformation-prerequisite virus receptors or of the actual viral cell entry process. Instead, post-receptor binding events [Na⁺/H⁺ exchange, Ga²⁺ flux, tyrosine phosphorylation of two proteins (55-601130-140 kd)] were Identified as critical determinants of transformability. The presence of competent virus In transformable cells was per se insufficient for transformation: blockade of Ca²⁺ fluxes (or the antiport) generates virus-loaded cells that express viral genes but remain untransformed. Delayed Induction by lonomycln of approprlately sized Ca²⁺ fluxes ([CaZ⁺], > 180 < 400 nM) re-starts transformation processes In EGTA-blocked, virus-loaded cells, perhaps providing a model for the study of virus re-activation. Overall, EBV Induces unique cellular activation events different from non-oncogenic lymphocyte mitogenslactivators, and, given the oncogenic potential of transformed cells In susceptible hosts, we hypothesize that these events describ a novel oncogenic transformaton pathway.