Structure and pathophysiology of the erythrocyte membrane-associated Paul-Bunnell heterophile antibody determinant in Epstein-Barr virus-associated disease.

Epstein-Barr virus (EBV), which was first isolated by Epstein, Barr, and Achong (1964) from a cultured Burkitt's lymphoma lymphoblast cell line, is the etiological agent for infections mononucleosis (IM), polyclonal oligoclonal lymphomas associated with primary and acquired immunodeficiencies, and the complications of X-linked lymphoproliferative syndrome (XLP) (Cantani and Mastrantoni, 1989; Englund, 1988; Ernberg et al., 1990; Jones and Straus, 1987; Okano et al., 1988; Purtilo et al., 1981; Shearer et al., 1985; Wilmes and Wolf, 1989). EBV also contributes to the pathogenesis of Burkitt's lymphoma (Frizzera, 1987; Harrington et al., 1988; Henle et al., 1968; Purtilo et al., 1981; Rowe et al., 1986; Saemundsen et al., 1981) and nasopharyngeal cancer (Pearson et al., 1984). Furthermore, people who have had IM have higher rates of subsequent development of malignant lymphoproliferative disorders (Abo et at., 1982; Snydman et al., 1982) and Hodgkin's disease (Green et al., 1979; Mueller, 1987; Poppema et al., 1985; Weiss et al., 1989), while patents with XLP have a higher incidence of non-Hodgkin's malignant lymphoma (Harrington et at., 1987). The precise role of EBV in these diseases is not well understood. Nonetheless, it is known that EBV infection triggers the formation of heterophile antibodies that, for many decades, have formed the basis for serologic diagnosis of IM. In this review, we discuss the discovery, species variation, and structure of the erythrocyte membrane-associated Paul-Bunnell (PB) heterophile antibody determinant, its implications to IM diagnosis, and its potential contribution to defective immune surveillance and associated uncontrolled proliferation of EBV-infected cells.