Analysis of genomic DNA and rna-transcripts of a heterohybridoma simultanously expressing IG3 and IgG1 with identical specificity

摘要

During the development of B-lymphocytes, the immunoglobulin heavy chain (lgH) gene undergoes two types of DNA recombinations. Joining of VDJ pieces of variable-region exons upstream of the C#mu# determines - beside somatic mutations - the specificity of the antibody (Ab). This first recombination event induces IgM specific immunogobulin expression. Further differentiation of B-cells leads to the production of other classes of IgH molecules through isotype switch on the IgH locus. The class switch recombination takes place between a pair of sites, one site on the intron between the JH and C#mu#, the other site in a region upstream of the later expressed CH gene. These recombination sites are variable and fall in or near the so-called switch (S)-regions. S-regions do not contain any conserved recombination signals, but are rich in repetitive sequences. Different models have been proposed to explain the subclass switch: recombination between homologs, unequal sister chromatide exchange, and looping out and deletion (Harrison et al., 1993). The deletion model is the simplest and most convincing explanation for class switch recombination. Circular DNA is excised from the chromosome, bringing subclass exons of gamma, alpha and epsilon specificity in proximity to the VDJ exons