Molecular Mechanism of Immunoglobulin Class Switch Recombination

Biological information is encoded in genomic DNA sequences that have been compiled during evolution. In addition to this innate information, individual mammals accumulate acquired information that includes learning andmemory in the nervous system and genetic rearrangements and mutations in the immune system. The immunesystem generates acquired information by (1) V(D)J recombination and somatic hypermutation to amplify V-region diversity and (2) class switch recombination (CSR)to diversify the manner whereby captured antigens areeliminated or the location where immunoglobulin (Ig) isdelivered and accumulated. CSR changes the Ig class expressed on B cells from IgM to one of the other classes(IgG, IgE, or IgA) by deleting, as a looped-out circle, theDNA sequences between the variable region (VH) geneand the constant region (CH) gene to be expressed afterthe switch (Honjo and Kataoka 1978; Cory et al. 1980;Rabbitts et al. 1980; Shimizu and Honjo 1984; Iwasato etal. 1990; Matsuoka et al. 1990; von Schwedler et al.1990). CSR appears to be unique among known recombination mechanisms because there are no consensus sequences for the sites of CSR (Nikaido et al. 1982; Dunnick et al. 1993; Lee et al. 1998) and because CSR takesplace between nonhomologous sequences in broad butdefined areas including and surrounding the S region(Dunnick et al. 1993; Lee et al. 1998), which is located 5′to each CH gene and composed of tandem arrays of shortrepetitive sequences (Shimizu et al. 1982)...