Immunoglobulin JH, Cμ, and CγGene Rearrangements in Human B Lymphocytes Clonally Transformed by Epstein--Barr Virus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 82; no. 2; pp. 556 - 560
• Main Authors: Brown, Nathaniel A., Liu, Chunren, Berenson, James R., Garcia, Charles R., Wang, Roger, Calame, Kathryn L.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.01.1985; National Acad Sciences
• Subjects: Alleles; B lymphocytes; B-Lymphocytes - immunology; Biological and medical sciences; Cell lines; Cell Transformation, Viral; Chromosome Deletion; Chromosomes; Clone Cells; Deoxyribonuclease BamHI; DNA - analysis; DNA probes; DNA Restriction Enzymes - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Genetic loci; Genetics of the immune response; Germ cells; Herpesvirus 4, Human; Humans; Immunobiology; Immunoglobulin constant regions; Immunoglobulin gamma-Chains - genetics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin J-Chains - genetics; Immunoglobulin mu-Chains - genetics; Mice; Nucleic Acid Hybridization; Virus; Human; Immunoglobulins; Gene; Herpesviridae; Gene rearrangement; Γ-Herpesvirinae; B-Lymphocyte; Epstein Barr virus; Cell transformation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.2.556

Somatic rearrangements and deletions of immunoglobulin gene segments have been demonstrated in several types of murine B cells. In addition, rearrangements of the JH, Cμ, and light chain immunoglobulin gene segments have been reported in human pre-B-cell leukemias and B-cell lymphomas. We have used recombinant DNA probes for the human JH, Cμ, and Cγimmunoglobulin gene loci to analyze the genetic events associated with heavy chain gene expression in human B cells clonally transformed by Epstein--Barr virus. Southern hybridization analysis of BamHI-digested cell clone DNAs shows that these human B-cell clones often have bi-allelic JHrearrangements and that heavy chain isotype switching is associated with bichromosomal Cμand Cγgene rearrangements. Deletions of germ line Cμand Cγsegments were observed that were sometimes bi-allelic. Overall, the observed rearrangements and deletions of heavy chain constant region genes suggest that human heavy chain class switching proceeds in a general order consistent with the proposed order of the heavy chain gene classes along chromosome 14.