Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes |
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Authors: | Tohru Kataoka Takashi Miyata Tasuku Honjo |
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Affiliation: | 1. Department of Genetics Osaka University Medical School Osaka 530, Japan;2. Department of Biology Faculty of Science Kyushu University Fukuoka 812, Japan |
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Abstract: | 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 γ2b gene from a mouse myeloma (MPC11) and compared its structure with the germ line counterparts. The rearranged γ2b gene contained the 5′ flanking region of the γ3 gene (Sγ3 region) which are linked to the 5′ flanking region of the γ2b gene (Sγ2b region). We have determined nucleotide sequences surrounding the recombination site of the rearranged and germ line γ2b genes, which include the Sγ2b and Sγ3 regions. Both γ2b and Sγ3 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 Sγ1 region in which class-switch recombination took place in MC101 myeloma. The nucleotide sequences of the Sγ1, Sγ2b and Sγ3 repeating units share significant homology with each other. The Sμ 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 Sγ regions. These results suggest that the recombination responsible for class switch from μ to γ or from a γ to another γ, may be facilitated directly or indirectly by homology of repeating sequences in S regions. |
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