Immunoglobulin JH, C mu, and C gamma gene rearrangements in human B lymphocytes clonally transformed by Epstein-Barr virus.

Somatic rearrangements and deletions of immunoglobulin gene segments have been demonstrated in several types of murine B cells. In addition, rearrangements of the JH, C mu, 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, C mu, and C gamma immunoglobulin 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 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. 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.