DNA sequences mediating class switching in alpha-immunoglobulins

Abstract

Immunoglobulin class switching involves specific DNA rearrangements of the gene segments coding for heavy chain constant regions (CH) during B lymphocyte differentiation. In two different cases of C mu to C alpha switching examined here (T15 and M603) and one taken from the literature (MC101), three different sites on the 5' side of C mu and three different sites on the 5' side of C alpha are joined together in the process of CH switching. The sequences surrounding the three germ-line C alpha sites of recombination are highly conserved blocks of 30 nucleotides that may serve as recognition sequences for CH switching to the C alpha gene. This putative recognition sequence is repeated 17 times in approximately 1400 nucleotides of the germ-line Calpha 5' flanking sequence. The lack of homology between this C alpha sequence and sequences reported for the C gamma 1 and C gamma 2b 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) CH switching progressed from C mu to C alpha to C gamma 1. This switching pathway may present difficulties for the simple deletional model of CH switching.