DNA sequences mediating class switching in alpha-immunoglobulins.
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.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005796:Genes; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D007136:Immunoglobulins / Q000235:genetics*; D051379:Mice; D009194:Myeloma Proteins / Q000235:genetics; D011995:Recombination, Genetic
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; D009194:Myeloma Proteins; D004247:DNA