Absence of IL‐6 receptor expression in fresh childhood Burkitt's lymphoma cells and induction of IL‐6 receptors by Epstein‐Barr virus in vitro

Abstract

Summary. Interleukin-6 (IL-6) is a cytokine which is necessary for the differentiation of activated B cells and growth of early haemopoietic progenitors. It is used for exvivo expansion of myeloid progenitors in the setting of highdose chemotherapy with autologous bone marrow transplantation (BMT). Expression of the IL-6 receptor (IL-6R) was examined in six fresh Burkitt's lymphoma (BL) cell preparations and 12 BL cell lines by reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry (FCM). Inducibility of IL-6R mRNA expression by EpsteinBarr virus (EBV) was studied by comparing two uninfected cell lines with the same cell lines infected by EBV. The phenotype of the BL cells lines was analysed by FCM and by proliferation assays in the presence of anti-IgM antibodies.None of the fresh BL cells expressed the IL-6 receptor. The BL cell lines expressed varying degrees of IL-6R mRNA and protein. In vitro infection of EBV-negative BL cell lines resulted in up-regulation of IL-6R mRNA. There was no proliferative response of the BL cell lines to IL-6, including the cells that expressed the receptor. Compared to uninfected BL cell lines, EBV-infected cell lines and lymphoblastoid cell lines (LCLs) showed a weaker or no response to anti-IgM antibodies, indicating a more mature phenotype of these cells. We conclude that the IL-6 receptor is not expressed in fresh childhood BLs, but only in BL cell lines. EBV infection in vitro leads to an up-regulation of IL-6R mRNA but not to increased proliferation. This makes growth stimulation of contaminating BL cells in the setting of autologous BMT unlikely.

Multiple Myeloma and B Cell Lymphoma. Investigation of IL-6, IL-6 Receptor Antagonist (IL-6RA), and GP130 Antagonist (GP130A) Using Various Parameters in anIn VitroModel

“…Tupitsyn et al [7] described that the majority of B cell tumours expressed either IL-6R or gp130. Tomeczkowski et al [8] and Klein et al [9] found IL-6 receptors only in B cell lymphoma cell lines infected by EBV. The membrane protein gp130 was expressed in all investigated MM cell lines and all B cell lymphoma cell lines.…”

Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease

“…Genes repressed by MPA in normal lymphocytes included interleukin 6 (IL-6) and IL-1. 41 The production of IL-6 acts as a proproliferative autocrine signal for in vitro EBV-transformed B cells, although whether this mechanism extends to primary BL cells remains controversial. [41][42][43][44] There is unconvincing evidence that IL-6 serves to support the survival of childhood BL, but there are a growing number of reports that indicate that this mechanism is a key feature of AIDS-related BL and other HIV-associated lymphoproliferative diseases.…”

“…41 The production of IL-6 acts as a proproliferative autocrine signal for in vitro EBV-transformed B cells, although whether this mechanism extends to primary BL cells remains controversial. [41][42][43][44] There is unconvincing evidence that IL-6 serves to support the survival of childhood BL, but there are a growing number of reports that indicate that this mechanism is a key feature of AIDS-related BL and other HIV-associated lymphoproliferative diseases. 42,43,45 In contrast, IL-1b is expressed by both EBV-transformed lymphoblastoid cell lines and BL cells and was shown to be upregulated by several EBV latent proteins.…”

Altered Gene Expression upon BCR Cross-Linking in Burkitt's Lymphoma B Cell Line

“…We detected gene expression of MDC, IL6R as well as SIRP␣, adhesion molecule LFA1, anti-apoptotic A-20, signal regulatory SLP76, and BCAR3, DNA binding proteins EGR2 and DEC1 in BCR cross-linked Burkitt's Lymphoma BL2 cell. It is known that MDC in unstimulated B cell lineage (8) and IL6R in BL2 cell line are not expressed (9,10). LFA1 molecule is significantly up-regulated upon B cell stimulation with anti-IgM and IL4 (11).…”