DNA Sequences Mediating Class Switching in α-Immunoglobulins
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 Cɑ 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_ɑ are joined together in the process of C_H switching. The sequences surrounding the three germ-line C_ɑ sites of recombination are highly conserved blocks of 30 nucleotides that may serve as recognition sequences for C_H switching to the C_ɑ gene. This putative recognition sequence is repeated 17 times in approximately 1400 nucleotides of the germ-line C_ɑ 5' flanking sequence. The lack of homology between this C_ɑ sequence and sequences reported for the C_(y1) and C_(y2b) 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_ɑ to C_(y1). This switching pathway may present difficulties for the simple deletional model of C_H switching.