genome-carrying cells in the circulation during IM was shown initially by the outgrowth of EBV-transformed lymphoblastoid cell lines from cultures of peripheral blood lymphocytes

Infectious mononucleosis (IM) 1 is a usually benign lymphoproliferative disease caused by Epstein-Barr virus (EBV) (1). Atypical lymphocytosis, the major hematologic abnormality of the disease, is due largely but not exclusively to the proliferation of immunologically activated T lymphocytes which are presumably reactive against EBV-infected lymphocytes (2, 3). Since EBV transforms resting human B lymphocytes in vitro into continuously dividing cells (4, 5), the effects of the virus on cells in vivo have major importance, especially in view of the association of EBV with Burkitt lymphoma, nasopharyngeal carcinoma (6), and immunoblastic lymphoma (7). Studies on EBV-infected cells in vivo have been limited. The presence of EBV genome-carrying cells in the circulation during IM was shown initially by the outgrowth of EBV-transformed lymphoblastoid cell lines from cultures of peripheral blood lymphocytes (8). It has been presumed that these cell lines originated from infected B lymphocytes because EBV has tropism for B cells in vitro, and cell lines from IM blood have B cell characteristics (9). However, these lines may not arise by direct outgrowth from circulating infected cells but from normal B cells secondarily infected by virus released in the culture (10). Lymphocytes expressing EB nuclear antigen (EBNA) have been seen in T cell-depleted peripheral blood lymphocytes during IM (11, 12), but these cells have not been further characterized. Thus, to date, direct evidence has been lacking that circulating EBV-infected cells are of B cell origin. Recently we reported the case of a 4-yr-old girl who developed fatal lymphoma during infectious mononucleosis (I 3). The tumor cells consisted of several populations of EBV-transformed B lymphoeytes which expressed EBNA and showed plasmacytic differentiation both by morphological characteristics and by the presence of cytoplasmic immunoglobulins detected by immunofluorescence. Several unusual features in this child suggested the presence of an immunodeficiency state permitting the uncontrolled proliferation of virus-altered cells. However, the plasmacytic nature of the EBNA-positive tumor cells suggested the possibility that the virus-induced lym-