EPSTEIN-BARR-VIRUS-ASSOCIATED LYMPHOPROLIFERATIVE SYNDROME IN SEVERE COMBINED IMMUNODEFICIENCY - ESTABLISHMENT OF A LYMPHOBLASTOID CELL-LINE AS AN IN-VITRO MODEL FOR BIOLOGICAL AND THERAPEUTIC STUDIES

Patients with primary or secondary immunodeficiency are at high risk f or B cell lymphoproliferative syndromes (LPS) that are generally Epste in-Barr virus (EBV)-associated, We established a cell line, termed JuW a, from an immunoblastic lymphoma that developed in a child with sever e combined immunodeficiency. JuWa cells mere representative of the ori ginal lymph node as shown by a similar IgH gene rearrangement pattern. The cell line exhibited the typical features of a lymphoblastoid cell line (LCL): (1) growth pattern in large clumps, (2) lack of structura l chromosome abnormalities, (3) type III latency with expression of EB V-associated EBNA2 and LMP, as well as B cell activation markers CD23 and CD30, thereby showing characteristics of an EBV producer cell line , i.e. a latent infection with a small subpopulation of cells spontane ously entering the lytic cycle, (4) inducibility of the lytic cycle by IdU and TPA, leading to an increase of early antigen and viral capsid antigen-positive cells from 1 to 15-20%, and (5) elimination of the l inear viral genomes by treatment with acyclovir (ACV), without affecti ng the circular episomal genomes. After withdrawal of ACV, viral repli cation resumed within 7 days. Thus, JuWa cells support the concept of the LCL-like features of LPS and lymphomas occurring in the setting of immunodeficiency. In our in vitro model, ACV treatment could effectiv ely suppress the viral replication but not cure EBV infection of B cel ls.