IMMUNOGLOBULIN JH, C-MU, AND C-GAMMA GENE REARRANGEMENTS IN HUMAN LYMPHOCYTES-B CLONALLY TRANSFORMED BY EPSTEIN-BARR VIRUS

Somatic rearrangements and deletions of Ig gene segments were demonstrated in several types of murine B cells. Rearrangements of the JH, C.mu. and light chain Ig gene segments are reported in human pre-B-cell leukemias and B-cell lymphomas. Recombinant DNA probes for the human JH, C.mu. and C.gamma. immunoglobulin gene loci were used 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 DNA shows that these human B-cell clones often have bi-allelic JH rearrangements and that heavy chain isotype switching is associated with bichromosomal C.mu. and C.gamma. gene rearrangements. Deletions of germ line C.mu. and C.gamma. segments were observed that were sometimes bi-allelic. The observed rearrangements and deletions of heavy chain contrast 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.