title: 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.
abstract: Patients with primary or secondary immunodeficiency are at high risk for B cell lymphoproliferative syndromes (LPS) that are generally Epstein-Barr virus (EBV)-associated. We established a cell line, termed JuWa, from an immunoblastic lymphoma that developed in a child with severe combined immunodeficiency. JuWa cells were representative of the original 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 structural chromosome abnormalities, (3) type III latency with expression of EBV-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 spontaneously 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 linear viral genomes by treatment with acyclovir (ACV), without affecting the circular episomal genomes. After withdrawal of ACV, viral replication 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 effectively suppress the viral replication but not cure EBV infection of B cells.
authors.affiliation: Abteilung für Pathologie, Universität Ulm, Deutschland.
authors.forename: M
authors.initials: M
authors.lastname: Simon
authors.forename: B
authors.initials: B
authors.lastname: Borisch
authors.forename: B
authors.initials: B
authors.lastname: Heymer
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000956:Antigens, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006566:Herpesviridae Infections / Q000150:complications* / Q000188:drug therapy; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D017403:In Situ Hybridization; D007223:Infant; D008198:Lymph Nodes / Q000166:cytology / Q000382:microbiology; D008214:Lymphocytes / Q000166:cytology; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000382:microbiology*; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000382:microbiology*; D013577:Syndrome
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D004279:DNA, Viral; D000212:Acyclovir