Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes

Immunoglobulin class switch involves a unique recombination event that takes place at the region 5' to each heavy chain constant region gene during B lymphocyte differentiation. Such regions that are responsible for the class-switch recombination are defined as S regions (Kataoka et al., Proc. Natl. Acad. Sci. USA 77, 919, 1980). We have cloned a rearranged gamma 2b gene from a mouse myeloma (MPC11) and compared its structure with the germ line counterparts. The rearranged gamma 2b gene contained the 5' flanking region of the gamma 3 gene (S gamma 3 region) which are linked to the 5' flanking region of the gamma 2b gene (S gamma 2b region). We have determined nucleotide sequences surrounding the recombination site of the rearranged and germ line gamma 2b genes, which include the S gamma 2b and S gamma 3 regions. Both gamma 2b and S gamma 3 regions comprise tandem repetition of conserved units of 49 bp. Similar 49 bp repeating units are also found in the previously determined sequence of the S gamma 1 region in which class-switch recombination took place in MC101 myeloma. The nucleotide sequences of the S gamma 1, S gamma 2b and S gamma 3 repeating units share significant homology with each other. The S mu region, partial nucleotide sequence of which was previously determined, contains abundant short sequences such as AGCT, TGGG and AGCTGGGG which are shared in common by repeating sequences in S gamma regions. These results suggest that the recombination responsible for class switch from mu to gamma or from a gamma to another gamma, may be facilitated directly or indirectly by homology of repeating sequences in S regions.