Activation of B lymphocytes by Epstein‐Barr virus/CR2 receptor interaction

Abstract

Epstein-Barr virus (EBV) infects and transforms human B lymphocytes. The virus receptor was shown to be identical to the complement receptor CR2. The consequences of EBV/CR2 receptor interaction on B lymphocyte activation were analyzed by infection of B cells with the transforming (B95-8) and the nontransforming (P3HR1) virus strains and with UV-inactivated B95-8 virus. Similar to mitogens and antibodies against surface IgM and CR2 receptor, transforming and nontransforming EBV induced the release of leukocyte migration inhibitory factor (LIF). LIF production occurred early after infection and was not affected by irradiation of the B95-8 virus with doses of UV-light which prevented the expression of viral functions. B lymphocytes infected with UV-inactivated virus responded to T cell-derived B cell growth factors. The results demonstrate that binding of EBV to the CR2 receptor activates the B cells. Progression of the infected cells in the activation pathway required helper cell-derived factors or signals provided by the intact viral genome. The nontransforming P3HR1 virus induced a low level of RNA synthesis and increase of cell size and major histocompatibility complex class I antigen expression. Only the transforming virus induced expression of EBV nuclear antigens and cellular DNA synthesis.

Activation of human platelets through gp140, the C3d/EBV receptor (CR2)

“…It appears from our data and from that of others that crosslinking of gp140, the C3d/EBVR, either at the cell surface of B lymphocytes by anti-gpl40 F(ab')z fragments [41], particlebound C3d [50], OKB-7, an anti-C3d/EBVR mAb [42] and UV-irradiated EBV [51] or at the cell surface of human platelets by anti-gpl40 IgG or C3d followed by anti-C3d F(ab')2 fragments, triggers cell activation in presence of other factors as T cell factors for B lymphocytes or as fibrinogen, thrombin or PAF-acether for human platelets. These data strongly support the conclusion that expression of gp140, the…”

Events Related to Epstein-Barr Virus Binding and Superinfection of Raji Cells

“…The binding to CR2 of multivalent ligands, as polymeric C3d/ C3dg or EBV, but not of monomeric ligands, leads to Bcell proliferation [3][4][5]. It is unknown whether the poly meric ligands induce cellular activation through dimer ization of the receptor or ligation of multiple epitopes of single CR2 molecules.…”

Epstein-Barr virus tissue tropism: a major determinant of immunopathogenesis

“…These observations are of particular interest to the biology of EBV since several independent studies have demonstrated that binding of the virus to its receptor provides the signal for at least a limited progression of the B cell into the cell cycle [7,38,53]. Thus, EBV has not only adapted to use a cell surface glycoprotein for attachment to the B cell surface, but it may also have evolved to mimic, in part, both the structure and function of the natural ligand.…”