Organization and Reorganization of Constant Region Genes of Immunoglobulin Heavy Chains: Genetic Basis for Class Switching

Honjo, Tasuku; Ishida, Norio; Kataoka, Tohru; Nakai, Sumiko; Nikaido, Toshio; Nishida, Yasuyoshi; Noma, Yoshihiko; Obata, Masahiro; Sakoyama, Yasuhiko; Shimizu, Akira; Takahashi, Naoki; Takeda, Shunichi; Ueda, Shintaro; Yamawaki-Kataoka, Yuriko; Yaoita, Yoshio

doi:10.1007/978-1-4684-4469-8_2

Tasuku Honjo²,
Norio Ishida²,
Tohru Kataoka²,
Sumiko Nakai²,
Toshio Nikaido²,
Yasuyoshi Nishida²,
Yoshihiko Noma²,
Masahiro Obata²,
Yasuhiko Sakoyama²,
Akira Shimizu²,
Naoki Takahashi²,
Shunichi Takeda²,
Shintaro Ueda²,
Yuriko Yamawaki-Kataoka² &
…
Yoshio Yaoita²

Part of the book series: Nobel Foundation Symposia Published by Plenum ((NOFS,volume 55))

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Summary

We have determined the complete organization of the mouse C_H gene family, which is comprised of the 8 C_H genes in the order 5’-J_H-6.5kb-C_μ-4.5kb-C_δ-55kb-C_γ3-34kb-C_γ1-21kb-C_γ2b-15kb-C_γ2a-14kb-C_ε-12kb-C_α-3’. The S regions, which contain characteristic tandemly repeated unit sequences, are located 5’ to each C_H gene except for the C_δ gene. There are at least two types of repetitive sequences dispersed in this 200 kb region. No pseudogenes are present. The arrangements of the C_H genes in BALB/c and C57BL mice are similar, but the lengths of the S regions vary. The basic structures of all the C_H genes are similar in that coding sequences are interrupted at the junctions of the domains and the hinge regions. Comparison of the nucleotide sequences of the C_H genes revealed that sequence segments have been exchanged among members of the C_H gene family. Cloning and characterization of human C_γ genes, i.e. C_γ1, C_γ2, C_γ3, C_γ4 and φC_γ, indicate that the human C_γ gene family evolved by dynamic DNA rearrangements, including gene duplication, exon duplication, and exon reassortment by unequal crossing-over. A human pseudo-epsilon gene (C_ε3) is a processed gene that has completely spliced out introns. The presence of movable genetic elements surrounding the C_ε3 gene suggests that the C_ε gene evolved by a translocation mechanism. Although S-S recombination has been shown to take place in myelomas and hybridomas secreting a large amount of immunoglobulin, analyses of the C_H gene organization in normal spleen B cells bearing immunoglobulin on their surface suggest that RNA splicing may be responsible for the first step in class switching, followed by S-S recombination. The nucleotide sequences of S regions contain short common sequences, TGGG(G) and (G)AGCT. Comparison of nucleotide sequences surrounding recombination sites revealed common sequences TGAG and TGGG. A sister chromatid exchange model was proposed to explain deletion of C_H genes accompanying S-S recombination. We have found that the S region serves as a preferred recombination site in E.coli extracts.

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Department of Genetics, Osaka University Medical School, Osaka 530, Japan
Tasuku Honjo, Norio Ishida, Tohru Kataoka, Sumiko Nakai, Toshio Nikaido, Yasuyoshi Nishida, Yoshihiko Noma, Masahiro Obata, Yasuhiko Sakoyama, Akira Shimizu, Naoki Takahashi, Shunichi Takeda, Shintaro Ueda, Yuriko Yamawaki-Kataoka & Yoshio Yaoita

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Tasuku Honjo
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Norio Ishida
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Sumiko Nakai
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Masahiro Obata
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Honjo, T. et al. (1983). Organization and Reorganization of Constant Region Genes of Immunoglobulin Heavy Chains: Genetic Basis for Class Switching. In: Möller, E., Möller, G. (eds) Genetics of the Immune Response. Nobel Foundation Symposia Published by Plenum, vol 55. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4469-8_2

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