Role of Epstein-Barr virus and soluble CD21 in persistent polyclonal B-cell lymphocytosis.

The expression of EBV proteins and immunological properties were studied in the first stable cell line (SM) established from a patient presenting with persistent polyclonal B-cell lymphocytosis (PPBL). SM cells which represent a small population of EBV-positive atypical cells found in the peripheral blood of the patient express the KI-1 antigen (CD30) as well as the protooncogene bcl-2 product and cell surface markers of mature activated B lymphocytes. The cells harbour an EBV subtype A genome and contain EBNA2 protein. This argues against a transformation-incompetent virus as the main cause of the chronic active EBV infection observed in our patient. Latent membrane protein (LMP1) was weakly expressed and found predominantly in a perinuclear localization, a location which could lead to decreased immunogenicity in vivo. Similar to the EBV-transformed marmoset cell line B95-8, SM cells were in part productively infected as transcription of the immediate early gene BZLF1 could be shown and in some cells high levels of EBV-genome were detected by in situ hybridization with a BamH1 W-probe. Comparable to the atypical cells in the peripheral blood of the patient, EBV small RNAs were not detected with EBER-specific probes. Of interest, we noticed a markedly increased production of soluble CD21 (sCD21) antigen by SM cells as compared to LCL-type Burkitt's lymphoma cell lines. This could explain the elevated sCD21 levels observed in the serum of our PPBL patient and confirms our previous findings in patients with acute EBV infection. It also suggests a possible role of sCD21 in EBV-mediated regulation of the immune response and provides a possible explanation for the dysregulation of the humoral immune system observed in PPBl patients.