Advertisement

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

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

Summary

We have determined the complete organization of the mouse CH gene family, which is comprised of the 8 CH genes in the order 5’-JH-6.5kb-Cμ-4.5kb-Cδ-55kb-Cγ3-34kb-Cγ1-21kb-Cγ2b-15kb-Cγ2a-14kb-Cε-12kb-Cα-3’. The S regions, which contain characteristic tandemly repeated unit sequences, are located 5’ to each CH gene except for the Cδ gene. There are at least two types of repetitive sequences dispersed in this 200 kb region. No pseudogenes are present. The arrangements of the CH genes in BALB/c and C57BL mice are similar, but the lengths of the S regions vary. The basic structures of all the CH 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 CH genes revealed that sequence segments have been exchanged among members of the CH gene family. Cloning and characterization of human Cγ genes, i.e. Cγ1, Cγ2, Cγ3, Cγ4 and φCγ, indicate that the human Cγ gene family evolved by dynamic DNA rearrangements, including gene duplication, exon duplication, and exon reassortment by unequal crossing-over. A human pseudo-epsilon gene (Cε3) is a processed gene that has completely spliced out introns. The presence of movable genetic elements surrounding the Cε3 gene suggests that the Cε 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 CH 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 CH genes accompanying S-S recombination. We have found that the S region serves as a preferred recombination site in E.coli extracts.

Keywords

Hinge Region Sister Chromatid Exchange Constant Region Recombination Site Class Switch Recombination 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alt, F.W., Rosenberg, N., Casanova, R.J., Thomas, E. and Baltimore, D. (1982) Nature 296, 325–331.PubMedCrossRefGoogle Scholar
  2. Baltimore, D. (1981) Cell 24, 592–594.PubMedCrossRefGoogle Scholar
  3. Barth, W.F., Mclaughlin, C.L. and Fahey, J.L. (1965) J. Immunol. 95, 781–790.PubMedGoogle Scholar
  4. Borges, M.S., Kumagai, Y., Okumura, K., Hirayama, N., Ovary, Z. and Tada, T. (1981) Immunogenetics 13, 499–507.PubMedCrossRefGoogle Scholar
  5. Cheng, H,-L., Blattner, F.R., Fitzmanrice, L., Mushinski, J.F. and Tucker, P.W. (1982) Nature 296, 410–415PubMedCrossRefGoogle Scholar
  6. Coleclough, C., Cooper, C. and Perry, R.P. (1980) Proc. Natl. Acad. Sci. USA 77, 1422–1426.CrossRefGoogle Scholar
  7. Cory, S. and Adams, J.M. (1980) Cell 19, 37–51.PubMedCrossRefGoogle Scholar
  8. Cory, S., Jackson, J. and Adams, J.M. (1980) Nature 285, 450–456.PubMedCrossRefGoogle Scholar
  9. Darnell, J.E. Jr, (1978) Science 202, 1257–1260.PubMedCrossRefGoogle Scholar
  10. Davis, M.M., Calame, K., Early, P.W., Livant, D.L., Joho, R., Weissman, I.L. and Hood, L. (1980a) Nature 283, 733–739.PubMedCrossRefGoogle Scholar
  11. Davis, M.M., Kim, S.K. and Hood, L. (1980b) Science 209, 1360–1365.PubMedCrossRefGoogle Scholar
  12. Dunnick, W., Rabbitts, T.H. and Milstein, C. (1980) Nature 286, 669–675.PubMedCrossRefGoogle Scholar
  13. Early, P., Rogers, J., Davis, M., Calame, K., Bond, M., Wall, R., and Hood, L. (1980) Cell 20, 313–319.PubMedCrossRefGoogle Scholar
  14. Edelman, G.M., Cunningham, B.A., Gall, W.E., Gottlieb, P.D., Rutishauser, U. and Waxdal, M.J. (1969) Proc. Natl. Acad. Sci. USA 63, 78–85.CrossRefGoogle Scholar
  15. Ellison, J., Buxbaum, J. and Hood, L. (1981) DNA 1, 11–18.PubMedCrossRefGoogle Scholar
  16. Ellison, J. and Hood, L. (1982) Proc. Natl. Acad. Sci. USA 79, 1984–1988.CrossRefGoogle Scholar
  17. Gilbert, W. (1978) Nature 271, 501.PubMedCrossRefGoogle Scholar
  18. Hollis, G.F., Hieter, P.A., McBride, O.W., Swan, D. and Leder, P. (1982) Nature 296, 321–325.PubMedCrossRefGoogle Scholar
  19. Honjo, T. and Kataoka, T. (1978) Proc. Natl. Acad. Sci. USA 75, 2140–2144.CrossRefGoogle Scholar
  20. Honjo, T., Obata, M., Yamawaki-Kataoka, Y., Kataoka, T., Kawakami, T., Takahashi, N. and Mano, Y. (1979) Cell 18, 559–568.PubMedCrossRefGoogle Scholar
  21. Honjo, T., Kataoka, T., Yaoita, Y., Shimizu, A., Takahashi, N., Yamawaki-Kataoka, Y., Nikaido, T., Nakai, S., Obata, M., Kawakami, T. and Nishida, Y. (1981a) Cold Spring Harbor Symp. Quant. Biol. 45, 913–923.CrossRefGoogle Scholar
  22. Honjo, T., Nakai, S., Nishida, Y., Kataoka, T., Yamawaki-Kataoka, Y., Takahashi, N., Obata, M., Shimizu, A., Yaoita, Y., Nikaido, T. and Ishida, N. (1981b) Immunol. Review 59, 33–67.CrossRefGoogle Scholar
  23. Hurwitz, J.L., Coleclough, C. and Cebra, J.J. (1980) Cell 22, 349–359.PubMedCrossRefGoogle Scholar
  24. Kalpaktsoglou, P.K., Hong, R. and Good, R.A. (1973) Immunol. 24, 303–314.Google Scholar
  25. Kataoka, T., Kawakami, T., Takahashi, N. and Honjo. T. (1980) Proc. Natl. Acad. Sci. USA 77, 919–923.CrossRefGoogle Scholar
  26. Kataoka, T., Miyata, T. and Honjo, T. (1981) Cell 23, 357–368.PubMedCrossRefGoogle Scholar
  27. Kataoka, T., Takeda, S. and Honjo, T. (1982) submitted.Google Scholar
  28. Kawakami, T., Takahashi N. and Honjo, T. (1980) Nucl. Acids Res. 8, 3933–3945.PubMedCrossRefGoogle Scholar
  29. Kishimoto, T., Shigemoto, S., Watanabe, T. and Yamamura, Y. (1979) J. Immunol. 123, 1039–1043.PubMedGoogle Scholar
  30. Kishimoto, T. (1982) Prog. Allergy (ed. P. Kailos, K. Ishizaka and B. Waksman) Kalger Pub. Inc., Basel, in press (1982).Google Scholar
  31. Lalanne, J.L., Bregegere, F., Abastado, J.P., Gachelin, G. and Kourilsky, P. (1982) Nucl. Acids Res. 10, 1039–1049.PubMedCrossRefGoogle Scholar
  32. Lefranc, G., Rivat, L., Sulier, J.P., van Loghem, E., Aydenian, H., Zalzal, P., Chakhachiro, L., Loiselet, K. and Ropartz, C. (1977) Am. J. Hum. Genet. 29, 523–536.PubMedGoogle Scholar
  33. Lawton, A.R., Kearney, J.F. and Cooper, M.D. (1977) Progress in Immunology 3, 171–182.Google Scholar
  34. Lerner, M.R., Boyk, J.A., Mount, S.M., Wolin, S.L. and Steitz, J.A. (1980) Nature 283, 220–224.PubMedCrossRefGoogle Scholar
  35. Liebhaber, S.A., Goossens, M. and Kan, Y.W. (1981) Nature 290, 26–29.PubMedCrossRefGoogle Scholar
  36. Liu, C.-P., Tucker, P.W., Mushinski, G.F. and Blattner, F.R. (1980) Science 209, 1348–1353.PubMedCrossRefGoogle Scholar
  37. Maki, R., Roeder, W., Traunecker, A., Sidman, C., Wabl, M., Raschke, W. and Tonegawa, S. (1981) Celi 24, 353–365.CrossRefGoogle Scholar
  38. Michaelsen, T.E., Frangione, B. and Franklin, E.D., (1977) J. Biol. Chem. 252, 883–399.PubMedGoogle Scholar
  39. Miyata, T., Yasunaga, T., Yamawaki-Kataoka, Y., Obata, M. and Honjo, T. (1980) Proc. Natl. Acad. Sci. USA 77, 2143–2147.CrossRefGoogle Scholar
  40. Moore, K.W., Rogers, J., Hunkapiller, T., Early, P., Nottenburg, C., Weissman, T., Bazin, H., Wall, R. and Hood, L.E. (1981) Proc. Natl. Acad. Sci. USA 78, 1800–1804.CrossRefGoogle Scholar
  41. Nakai, S., Vernon, O., Herzenberg, L.A., Yamagishi, H., and Honjo, T. (1982) Biomed. Res. 3, 37–45.Google Scholar
  42. Natvig, J.B., Kunkel, H.G. and Litwin, S.D. (1967) Cold Spring Harbor Symp. on Quant. Biol. 32, 173–180.Google Scholar
  43. Nikaido, T., Nakai, S. and Honjo, T. (1981) Nature 292, 845–848.PubMedCrossRefGoogle Scholar
  44. Nikaido, T., Yamawaki-Kataoka, Y. and Honjo, T. (1982) J. Biol. Chem. 257, 7322–7329.PubMedGoogle Scholar
  45. Nilsson, K. (1971) Int. J. Cancer 7, 380–396.PubMedCrossRefGoogle Scholar
  46. Nishida, Y., Kataoka, T., Ishida, N., Nakai, S., Kishimoto, T., Böttcher, I. and Honjo, T. (1981) Proc. Natl. Acad. Sci. USA 78, 1581–1585.CrossRefGoogle Scholar
  47. Nishida, Y., Miki, T., Hisajima, H. and Honjo, T. (1982) Proc. Natl. Acad. Sci. USA 79, 3833–3837.CrossRefGoogle Scholar
  48. Nishioka, Y., Leder, A. and Leder, P. (1980) Proc. Natl. Acad. Sci. USA 77, 2806–2809.CrossRefGoogle Scholar
  49. Nottenberg, C. and Weisman, I.L. (1981) Proc. Natl. Acad. Sci. USA 78, 484–488 (1981).CrossRefGoogle Scholar
  50. Obata, M., Kataoka, T., Nakai, S., Yamagishi, H., Takahashi, N., Yamawaki-Kataoka, Y., Nikaido, T., Shimizu, A. and Honjo, T. (1981) Proc. Natl. Acad. Sci. USA 78, 2437–2441.CrossRefGoogle Scholar
  51. Ollo, R. and Rougeon, F. (1982) Nature 296, 761–763.PubMedCrossRefGoogle Scholar
  52. Perlmutter, A. P. and Gilbert, W. (1982) Proc. Natl. Acad. Sci. USA, in press.Google Scholar
  53. Pink, J.R.L., Buttery, S.H., deVries, G.M. and Milstein, C. (1970) Biochem. J. 117, 33–47.PubMedGoogle Scholar
  54. Rabbitts, T.H., Forster, A., Dunnick, W. and Bentley, D.L. (1980) Nature 283, 351–356.PubMedCrossRefGoogle Scholar
  55. Rabbitts, T.H., Forster, A. and Milstein, C. (1981) Nucl. Acids Res. 9 4509–4524.PubMedCrossRefGoogle Scholar
  56. Ravetch, J.V., Kirsch, I.R. and Leder, P. (1980) Proc. Natl. Acad. Sci. USA 77, 6734–6738.CrossRefGoogle Scholar
  57. Razin, A. and Riggs, A.D. Science 210, 604–610 (1980).PubMedCrossRefGoogle Scholar
  58. Roeder, W., Maki, R., Traunecker, A. and Tonegawa, S. (1981) Proc. Natl. Acad. Sci. USA 78, 474–478.CrossRefGoogle Scholar
  59. Rogers, J., Early, P., Carter, C., Calame, K., Bond, M., Hood, L. and Wall, R. (1980) Cell 20, 303–312.PubMedCrossRefGoogle Scholar
  60. Rogers, J. and Wall, R. (1980) Proc. Natl. Acad. Sci. USA 77, 1877–1879.CrossRefGoogle Scholar
  61. Rogers, J., Choi, E., Souza, L., Carter, C., Word, C., Kuehl, M., Eisenberg, D. and Wall, R. (1981) Cell 26, 19–27.PubMedCrossRefGoogle Scholar
  62. Rogers, J. and Wall, R. (1981) Proc. Natl. Acad. Sci. USA 78, 7497–7501.CrossRefGoogle Scholar
  63. Sakano, H., Maki, R., Kurosawa, Y., Roeder, W. and Tonegawa, S. (1980) Nature 286, 676–683.PubMedCrossRefGoogle Scholar
  64. Sakoyama, Y., Yaoita, Y. and Honjo, T. (1982) Nucl. Acids Res. in press.Google Scholar
  65. Schrier, P.H., Bothwell, A.L.M., Mueller-Hill, B. and Baltimore, D. (1981) Proc. Natl. Acad. Sci. USA 78, 4495–4497.CrossRefGoogle Scholar
  66. Sher, I., Ahmed, A., Strong, D.M., Steinberg, A.D. and Paul, W.E. (1975) J. Exp. Med. 141, 788–803.Google Scholar
  67. Shimizu, A., Takahashi, N., Yamawaki-Kataoka, Y., Nishida, Y., Kataoka, T. and Honjo, T. (1981) Nature 289, 149–153.PubMedCrossRefGoogle Scholar
  68. Shimizu, A., Takahashi, N., Yaoita, Y. and Honjo, T. (1982a) Cell 28, 499–506.PubMedCrossRefGoogle Scholar
  69. Shimizu, A., Hamaguchi, Y., Yaoita, Y., Moriwaki, K., Kondo, K. and Honjo, T. (1982b) Nature 298, 82–84.PubMedCrossRefGoogle Scholar
  70. Sitia, R., Rubartelli, A. and Hammerling, U. (1981) J. Immunol. 127, 1388–1394.PubMedGoogle Scholar
  71. Slightom, J.L., Blechl, A.E. and Smithies, O. (1980) Cell 21, 627–638.PubMedCrossRefGoogle Scholar
  72. Smith, G.R., Kunes, S.M., Schultz, D.W., Taylor, A. and Trinan, K.L. (1981) Cell 24 429–436.PubMedCrossRefGoogle Scholar
  73. Takahashi, N., Kataoka, T. and Honjo, T. (1980a) Gene 11, 117–127.PubMedCrossRefGoogle Scholar
  74. Takahashi, N., Nakai, S. and Honjo, T. (1980b) Nucl. Acids Res. 8, 5983–5991.PubMedCrossRefGoogle Scholar
  75. Takahashi, N., Shimizu, A., Obata, M., Nishida, Y., Nakai, S., Nikaido, T., Kataoaka, T., Yamawaki-Kataoka, Y., Yaoita, Y., Ishida, N. and Honjo, T. (1981) C. Janeway, E.E. Sercarz and H. Wigzell, eds. ( New York: Academic Press ), pp 123–134.Google Scholar
  76. Takahashi, N., Ueda, S., Obata, M., Nikaidd, T. and Honjo, T. (1982) Cell 29, 671–679.PubMedCrossRefGoogle Scholar
  77. Tucker, P.W., Liu, C.-P., Mushinski, J.F. and Blattner, F.R. (1980) Science 209, 1353–1360.PubMedCrossRefGoogle Scholar
  78. Tucker, P.W., Slighton, J.L. and Blattner, F.R. (1981) Proc. Natl. Acad. Sci. USA 78, 7684–7688.CrossRefGoogle Scholar
  79. Tyler, B.M., Cowman, A.F., Gerondakis, S.D., Adams, J.M. and Bernard, O. (1982) Proc. Natl. Acad. Sci. USA 79, 2008–2012.CrossRefGoogle Scholar
  80. van der Loo, W., Gronowicz, E.S., Strober, S. and Herzenberg, L.A. (1979) J. Immunology 122, 1203–1208.Google Scholar
  81. Wang, An-Chuan, Tung, E. and Fudenberg, H. (1980) J. Immunol. 125, 1048–1054.PubMedGoogle Scholar
  82. Wilde, C.D., Crowther, C.E., Cripe, T.P., Lee, M. G.-S. and Cowan, N.J. (1982) Nature 297, 83–84.PubMedCrossRefGoogle Scholar
  83. Yamawaki-Kataoka, Y., Kataoka, T., Takahashi, N., Obata, M. and Honjo, T. (1980) Nature 283, 786–789.PubMedCrossRefGoogle Scholar
  84. Yamawaki-Kataoka, Y., Miyata, T. and Honjo, T. (1981) Nucl. Acids Res. 9, 1365–1381. PubMedCrossRefGoogle Scholar
  85. Yamawaki-Kataoka, Y., Nakai, S., Miyata, T. and Honjo, T. (1982) Proc. Natl. Acad. Sci. USA 79, 2623–2627.PubMedCrossRefGoogle Scholar
  86. Yaoita, Y. and Honjo, T. (1980a) Biomed. Res. 1, 164–175.Google Scholar
  87. Yaoita, Y. and Honjo, T. (1980b) Nature 286, 850–853.PubMedCrossRefGoogle Scholar
  88. Yaoita, Y., Kumagai, Y., Okumura, K. and Honjo, T. (1982) Nature 297, 697–699.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Tasuku Honjo
    • 1
  • Norio Ishida
    • 1
  • Tohru Kataoka
    • 1
  • Sumiko Nakai
    • 1
  • Toshio Nikaido
    • 1
  • Yasuyoshi Nishida
    • 1
  • Yoshihiko Noma
    • 1
  • Masahiro Obata
    • 1
  • Yasuhiko Sakoyama
    • 1
  • Akira Shimizu
    • 1
  • Naoki Takahashi
    • 1
  • Shunichi Takeda
    • 1
  • Shintaro Ueda
    • 1
  • Yuriko Yamawaki-Kataoka
    • 1
  • Yoshio Yaoita
    • 1
  1. 1.Department of GeneticsOsaka University Medical SchoolOsaka 530Japan

Personalised recommendations