Epstein--Barr Virus-Transformed Pro-B Cells are Prone to Illegitimate Recombination between the Switch Region of the μ Chain Gene and Other Chromosomes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 16; pp. 6333 - 6337
• Main Authors: Altiok, Ender, Klein, George, Zech, Lore, Uno, Masatsune, Henriksson, Barbro Ehlin, Battat, Shosh, Ono, Yasushi, Ernberg, Ingemar
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1989; National Acad Sciences
• Subjects: Antigens; B lymphocytes; B-Lymphocytes - immunology; Biological and medical sciences; Blotting, Southern; Cell Line; Cell lines; Cell Transformation, Viral; Chromosome translocation; Chromosomes; Chromosomes, Human; DNA probes; Epstein-Barr virus; Fundamental and applied biological sciences. Psychology; Gene Rearrangement, B-Lymphocyte; Genes; Genes, Immunoglobulin; Genic rearrangement. Recombination. Transposable element; Herpesvirus 4, Human - genetics; Humans; Immunoglobulin genes; Immunoglobulin mu-Chains - genetics; Immunoglobulins; Karyotyping; Molecular and cellular biology; Molecular genetics; Recombination, Genetic; T cell antigen receptors; Translocation, Genetic; Gammaherpesvirinae; Translocation; Immunoglobulins; Recombination; Herpesviridae; Transformed cell; Chromosome; B-Lymphocyte; Epstein Barr virus; Precursor; Virus; Immunogenetics; heavy-»Peptide chain; Gene; Gene rearrangement
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.16.6333

Six independently maintained sublines of FLEB 14, a fetal-liver-derived Epstein--Barr virus-transformed pro-B cell line that has not yet rearranged its immunoglobulin genes, were examined after in vitro propagation during 19-36 months. Two lines showed no immunoglobulin heavy chain gene rearrangement, whereas one allele was rearranged with breakpoints inside the switch region of the μ chain gene in the remaining four. These rearrangements had been generated by the translocation of different chromosome fragments to the immunoglobulin heavy chain gene cluster-carrying 14q32 band in each of the four lines. Previously, a similar rearrangement was found in a fifth subline concurrently with a reciprocal 6;14 translocation. The transposed pieces have been derived from chromosomes 16 and 18 in two of the more recently rearranged lines. Their origins could not be determined in the remaining two lines, but they were different from each other and the other three 14q+ markers. The 14q+ marker-carrying variant has replaced its diploid progenitor suggesting that the translocation has conveyed some in vitro growth advantage on its carrier. This was also supported by the duplication of the 14q+ marker and the loss of its normal chromosome 14 homologue in one subline during serial culturing. The vulnerability of the switch region of the μ chain gene to illegitimate recombination at the pro-B stage and the possible relevance of this finding for the origin of the Burkitt lymphoma-associated 8;14 (immunoglobulin heavy chain gene cluster/MYC) translocation is discussed.