Human immunoglobulin heavy chain genes: evolutionary comparisons of Cμ, Cδ and Cγ genes and associated switch sequences

Abstract

Human immunoglobulin heavy chain constant region genes have been characterised in isolated clones. The human Cμ gene comprises discrete domains for Cμ1, Cμ2, Cμ3 and Cμ4 + tp separated by short intervening sequences. The Cδ gene has been located about 5 kb downstream of Cμ4. Furthermore, the coding segments for the membrane form of μ have been located 1.9 kb downstream of Cμ4. Tandemly repeated sequences implicated in the heavy chain class switch occur upstream of the Cμ and the Cγ genes, but none were detected near the Cδ gene. These tandem repeats are very homologous to those of mouse. Particularly common is the sequence G-A-G-C-T. These data suggest that the μ to γ switch in humans involves DNA rearrangements of the CH-genes and subsequent deletion of DNA, but that the coexpression of Cμ and Cδ genes results from different mechanisms.