Immunoglobulin gene rearrangements and deletions in human Epstein-Barr virus-transformed cell lines producing different IgG and IgA subclasses

Abstract

During differentiation B lymphocytes may switch from the expression of surface IgM to the synthesis of IgG, IgA, or IgE isotypes by using a different heavy chain constant region (CH) gene. The molecular mechanisms by which switching occurs remain controversial. Rearrangements and deletions of CH genes 5' to the expressed gene have often been observed in the mouse and, more recently, in human cells that have switched isotypes. We have used human JH, C micro, C gamma, and C alpha probes to examine the extent of the deletions and rearrangements in clones of Epstein-Barr virus-transformed human cells that produce IgG1, IgG3, IgG4, or IgA1. Though deletions of CH genes 5' to the expressed CH gene were consistently observed, the rearrangement process appeared to be highly variable for the nonproductive CH gene locus: deletion or persistence of 5' CH genes, combinations of deletion and duplication of 5' genes, and deletions extending to 3' CH genes. Our results reveal an unexpected lack of specificity in the DNA deletions in cells that have undergone isotype switching.