IN-VITRO CULTURE OF B-LYMPHOCYTES DERIVED FROM EPSTEIN-BARR-VIRUS-ASSOCIATED POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE - CYTOKINE PRODUCTION AND EFFECT OF INTERFERON-ALPHA

Epstein-Barr-virus-associated posttransplant lymphoproliferative disea se ranges from transient lymphadenitis to aggressive lymphoma. This st udy characterizes an in vitro model to study the pathogenesis of this disease with a cell culture system. Five B-cell lines derived from pos ttransplant lymphoproliferative disease tissue were characterized with regard to immunophenotype, karyotype, molecular genetics, cytokine pr oduction, and growth regulation. All cell lines expressed CD19, CD21, CD22, CD43, and CD77, but not CD10 antigens. Immunoglobulin light chai n restriction was seen in four of five cell lines, and cytogenetic abn ormalities were demonstrable in three of the five. Cells proliferating in culture contained multiple Epstein-Barr virus episomes and showed lytic viral replication. All cell lines produced tumor necrosis factor -beta and interleukin-10 without evidence of autocrine growth regulato ry loops involving these cytokines. No evidence of IL-1 alpha, IL-2, I L-4, IL-5 or IL-6 production was found by reverse transcriptase polyme rase chain reaction. Adding 500 U IFN-alpha/ml to the culture medium r esulted in 30% inhibition of [H-3]thymidine incorporation.