Circular DNA is a product of the immunoglobulin class switch rearrangement (original) (raw)

Nature volume 345, pages 452–456 (1990)Cite this article

Abstract

THE class of immunoglobulin is defined by the constant region of its heavy chain. When a B lymphocyte switches the class of heavy chain it produces, the constant region of _µ_-type heavy chain is replaced (reviewed in refs 1 and 2, and see ref. 3); this occurs through a DNA rearrangement that brings the gene segment encoding the new constant region close to the VDJ segment encoding the variable region. The pre-B-cell line 18-81, which switches from heavy chain µ to _γ_2b production in culture4,5, occasionally abnormally rearranges the heavy chain locus so that DNA sequences between the switch regions of µ and _γ_2b are inverted6. Because looping-out is an intermediate step in generating an inversion, the switch rearrangement could occur by looping-out and deletion. Provided that recombination is reciprocal, this would produce a circle of DNA. Indeed, circular DNA molecules have been isolated as products of rearrangement among gene segments encoding the variable regions of the T-cell receptor7,9 and of the immunoglobulin heavy chain10,11 and light chain11,12. But whereas the breakpoints for the variable region rearrangement are precisely defined, the breakpoints for any given heavy chain class switch are scattered over a length of >6 kilobases, including both switch regions. We have now isolated circular DNA containing the sequences deleted by class-switching, thereby showing that the immunoglobulin heavy chain class switch occurs through looping-out and deletion.

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References

  1. 1. Shimizu A & Honjo T Cell 36, 801 803 (1984) 2. Marcu K B Cell 29, 719-721 (1982) 3. Shimizu A Takahashi N Yaoita Y & Honjo T Cell 28, 499 506 (1982) 4. Burrows P D Beck G B & Wabl M R Proc natn Acad Sei USA 78, 564 568 (1981) 5. Burrows P D Beck Engeser G B & Wabl M R Nature 306, 243-246 (1983) 6. Jack H M McDowell M Steinberg C M & Wabl M Proc natn Acad Sei USA 85,1581 1585 (1988) 7. Fujimoto S & Yamagishi H Nature 327, 242 243 (1987) 8. Okazaki K Davis D D & Sakano H Cell 49, 477 485 (1987) 9. Okazaki K & Sakano H EMBO J 7,1669 1674 (1988) 10. Abe M & Shiku H Nucleic Acids Res 17,163 170 (1989) 11. Toda M Hirama T Takeshita S & Yamagishi H Immun Lett 21, 311 316 (1989) 12. McCormack W T ei al Cell 56, 785 791 (1989) 13. Kearney J F & Lawton A R J Immun 115, 671 681 (1975) 14. Pernis B Forni L & Luzzati A L Cold Spring Harb Symp quant Biol 41,175 183 (1976) 15. Wabl M R Form L & Loor F Science 199,1078 1080 (1978) 16. Griffin B E Bjorck E Bjursell G & Lmdahl T J Virol 40,11 19 (1981) 17. Carroll S M er Molec cell Biol 7,1740 1750 (1987) 18. Kataoka T Miyata T & Honjo T Cell 23, 357-368 (1981) 19. Sakano H Maki R Kurosawa Y Roeder W & Tonegawa S Nature 286, 676 683 (1980) 20. Obata M ef Proc natn Acad Sei USA 78, 2437 2441 (1981) 21. Tilley S A & Birshtem B K J exp Meu 162, 675 694 (1985) 22. Altiok E et Proc natn Acad Sei USA 86, 6333 6337 (1989) 23. Durdik J et Proc natn Acad Sei USA 86, 2346 2350 (1989) 24. Wabl M Meyer J Beck Engeser G Tenkhoff M & Burrows P D Nature 313,687 689 (1985) 25. Kindt T J Mandy W J & Todd C W Biochemistry 9, 2028 2032 (1970) 26. Landucci Tos; Mage R G & Dubiski S J Immun 104, 641 647 (1970) 27. Kmght K L & Hanly W C Contemp Top molec Immun 4. 55 58 (1975) 28. Pernis B et al Immunochemistry 10, 281-285 (1973) 29. Gearhart P J Hurwitz J L & Cebra J J Proc natn Acad Sei USA 77, 5424-5428 (1980) 30. Seldm M F Howard T A & D Eustachio P Genomics 5, 24-28 (1989) 31. Alt F W & Yancopoulos G D Nature 327,189-190 (1987)

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  1. Laboratory of Radiobiology and Environmental Health, and Department of Microbiology and Immunology, University of California, San Francisco, California, 94143-0414, USA
    Uta von Schwedler, Hans-Martin Jck & Matthias Wabl

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  1. Uta von Schwedler
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  2. Hans-Martin Jck
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  3. Matthias Wabl
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von Schwedler, U., Jck, HM. & Wabl, M. Circular DNA is a product of the immunoglobulin class switch rearrangement.Nature 345, 452–456 (1990). https://doi.org/10.1038/345452a0

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