Molecular characterization of an unusual non-Hodgkin's B-lymphoma cell line ("Farage") lacking the ability to produce immunoglobulin polypeptide chains

Abstract

"Farage" is a cell line derived from a patient who had a diffuse and mixed type malignant lymphoma. In a previous study it was shown that Farage cells expressed B-cell markers, but not membrane IgM. Karyotypic analysis showed that in contrast to most follicular cell lymphomas, Farage did not have the 14;18 chromosomal translocation. In the present work Farage was further characterized by Southern and Northern blot analyses. Two rearranged heavy chain alleles and one rearranged kappa chain gene were detected. The cells expressed both mu and kappa mRNA, even though at a 3-7 fold lower level than that found in the control Daudi and DG-75 Burkitt lymphomas. Farage cells did not express the terminal deoxynucleotydyl transferase gene (TdT), nor the recombination activating genes RAG-1 and RAG-2, known as markers of the pre-B cell stage. These results show that Farage represents a mature B-cell rather than a pre-B cell. Despite the presence of C kappa and C mu RNAs, no Ig polypeptide chains were produced by Farage as judged by immunoblotting and biosynthesis labeling assays. Ig mRNAs were detected on the polysomal fraction, but at a lower level relative to Daudi cells. Our combined results suggest that in Farage cells translation of Ig mRNA is not fully blocked at the stage of translation initiation. Farage cells may express "germline" or mutated variants of Ig mRNAs. The unusual phenotype of Farage may reflect a normal as yet unknown stage of B-cell differentiation, or it may be due to an aberrant expression developed after malignant transformation.