DNA Sequences Mediating Class Switching in α-Immunoglobulins

Abstract

Immunoglobulin class switching involves specific DNA rearrangements of the gene segments coding for heavy chain constant regions (C H ) during B lymphocyte differentiation. In two different cases of C μ to C α switching examined here (T15 and M603) and one taken from the literature (MC101), three different sites on the 5′ side of C μ and three different sites on the 5′ side of C α are joined together in the process of C H switching. The sequences surrounding the three germ-line C α sites of recombination are highly conserved blocks of 30 nucleotides that may serve as recognition sequences for C H switching to the C α gene. This putative recognition sequence is repeated 17 times in approximately 1400 nucleotides of the germ-line C α 5′ flanking sequence. The lack of homology between this C α sequence and sequences reported for the C γ1 and C γ2b switch sites suggests that heavy chain switching is mediated by class-specific recognition sequences and, presumably, class-specific regulatory mechanisms. In addition, it appears that in one example (MC101) C H switching progressed from C μ to C α to C γ1 . This switching pathway may present difficulties for the simple deletional model of C H switching.