Molecular aspects of heavy-chain class switching.
Ig heavy chain class switching results from recombination that specifically joins together tandemly repeated sequences called S-regions. S-regions are located 5' of every CH gene except C delta. Recombination between S mu and a downstream S-region results in the juxtaposition of the rearranged variable region genes with C gamma, C epsilon, or C alpha genes and expression of the new isotype. Switch recombination is probably mediated by specific recombinase(s) that may be involved in other types of Ig-gene recombination. The efficiency and regulation of class-switch recombination is influenced by a number of factors, both structural and functional. Structurally, S-regions are all composed of tandemly repeated sequences that contain common pentamer sequences, but they differ in their length and their degree of sequence similarity with S mu. The mechanism of switching appears to be influenced by the accessibility of the S-region to recombinase(s). The conformational changes that result in accessibility are unknown but are correlated with transcription and hypomethylation of DNA near S-regions. Torsional stress resulting from progression of RNA polymerase through a GC-rich S-region could serve to further distort the DNA conformation and open the duplex, thus making it available for DNA strand invasion and recombinase activity. Although the mechanistic events of S-S recombination remain to be elucidated, switching is clearly influenced by protein mediators (mitogens and interleukins) which induce differential transcription of S regions.
Gritzmacher
C A
CA
Division of Molecular Biology, Medical Biology Institute, La Jolla, California.
D000818:Animals; D000916:Antibody Diversity; D001483:Base Sequence; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D015321:Gene Rearrangement; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007134:Immunoglobulin Switch Region; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D012326:RNA Splicing; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D045567:VDJ Recombinases
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007135:Immunoglobulin Variable Region; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases