In vitro transformation by Epstein-Barr virus induces a switch in growth factor and anti-IgM responsiveness in a human leukemic B cell clone.
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 beta, (TGF-beta)] 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-beta, 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-beta 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.
Janssen
O
O
Institute of Immunology, University of Heidelberg, FRG.
Gillis
S
S
Kabelitz
D
D
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015291:Transforming Growth Factors / Q000494:pharmacology
D015703:Antigens, CD; D007075:Immunoglobulin M; D007376:Interleukin-2; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D015291:Transforming Growth Factors