MOLECULAR CHARACTERIZATION OF AN UNUSUAL NON-HODGKINS B-LYMPHOMA CELL-LINE (FARAGE) LACKING THE ABILITY TO PRODUCE IMMUNOGLOBULIN POLYPEPTIDE-CHAINS

''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. Karyotypi c analysis showed that in contrast to most follicular cell lymphomas, Farage did not have the 14;18 chromosomal translocation. In the presen t 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 D audi and DG-75 Burkitt lymphomas. Farage cells did not express the ter minal deoxynucleotydyl transferase gene (TdT), nor the recombination a ctivating genes RAG-1 and RAG-2, known as markers of the pre-B cell st age. 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 I g polypeptide chains were produced by Farage as judged by immunoblotti ng and biosynthesis labeling assays. Ig mRNAs were detected on the pol ysomal fraction, but at a lower level relative to Daudi cells. Our com bined results suggest that in Farage cells translation of Ig mRNA is n ot 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-cel l differentiation, or it may be due to an abberant expression develope d after malignant transformation.