Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals.

Abstract

Immunoglobulin (Ig) heavy chain class switch recombination has been studied at the DNA level in a non-mammalian vertebrate, the amphibian Xenopus. A switch (S) region of about 5 kb has been identified in the JH-C mu intron of the Ig heavy chain locus in Xenopus. S mu contains 23 repeats approximately 150 bp long. Each repeat consists of internal shorter repeats and palindromic sequences, such as AGCT, which they share with mammalian switch regions. A deletion of the mu gene and the joining of the S regions of mu and chi occurs in B cells expressing IgX, one of the two non-mu isotypes in Xenopus. S chi shows no sequence homology with S mu and is characterized by 16 and 121 bp repeats and a high frequency of CATG, AGCA and TGCA palindromes. Both IgM and IgX S regions are AT rich and not GC rich like mammalian S regions. Recombination occurs, most of the time, at positions (microsites) where a single-stranded DNA folding program predicts the transition from a stem to a loop structure. This feature is conserved in most mammalian switch junctions which points to the general existence and involvement of microsites at one step of the determination of the recombination break-point. The recombinogenic nature of the switch regions is therefore linked to its structure rather than to its base composition, the repetitive occurrence of palindromes being essential at creating many microsites.