In vitro transformation by Epstein-Barr virus induces a switch in growth factor and anti-IgM responsiveness in a human leukemic B cell clone

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Abstract
By in vitro transformation with Epstein‐Barr virus (EBV), we have previously established EBV lymphoblastoid cell lines (LCL) from a patient with leukemic centrocytic B cell lymphoma. EBV‐transformed LCL and EBV genome‐negative leukemic B cells showed identical chromosome aberrations and IgH gene rearrangements. In the present study we have analyzed the effect of exogenous cytokines [interleukin (IL) 1, 2, 3, 4, 6, tumor necrosis factor, lymphotoxin, transforming growth factor β, (TGF‐β)] and anti‐IgM antibodies on the in vitro proliferation of EBV− leukemic B cells and EBV‐converted LCL. In contrast to conventional chronic lymphocytic leukemia, B cells of the patient DUL spontaneously proliferated for up to two weeks in the absence of exogenous lymphokines. The spontaneous proliferative capacity of clonal DUL B cells was not modulated by IL 1, IL 3, IL 6, TNF or LT. In vitro growth of DUL B cells was increased, however, by exogenous recombinant (r)IL 2, and was abrogated by TGF‐β, rIL 4 and anti‐IgM. rIL 4 not only inhibited spontaneous B cell proliferation but also neutralized the enhancing effect of rIL 2. In contrast, growth of the EBV‐transformed DUL LCL was not affected by any of these factors. These data demonstrate that in vitro infection and transformation of a clonal B cell population by EBV induces a switch in responsiveness to rIL 4, TGF‐β and anti‐IgM. In addition, this report is the first to demonstrate an inhibitory effect of rIL 4 on a spontaneously proliferating human leukemic B cell clone.