Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1980 Feb;77(2):1106–1110. doi: 10.1073/pnas.77.2.1106

Organization of kappa light chain genes in germ-line and somatic tissue.

R Joho, I L Weissman, P Early, J Cole, L Hood
PMCID: PMC348433  PMID: 6244580

Abstract

We studied the organization of the kappa light chain genes in germ-line (sperm) and somatic (embryo) tissues. We constructed a plasmid containing a DNA insert coding for the kappa chain MOPC 167 and used the Southern blotting technique to determine the organization of kappa variable and constant region genes. In the haploid genome of the mouse there is only one constant region gene detectable and it has the same organization in sperm and embryo DNAs. There are several variable region genes in sperm and embryo that are related to the Vk167 gene. The organization of the V genes in sperm and embryo DNAs is identical. These results show that there is no rearrangement of variable region genes (or "minigenes") during early embryogenesis.

Full text

PDF
1106

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brenner S., Milstein C. Origin of antibody variation. Nature. 1966 Jul 16;211(5046):242–243. doi: 10.1038/211242a0. [DOI] [PubMed] [Google Scholar]
  3. Burstein Y., Schechter I. Primary structures of N-terminal extra peptide segments linked to the variable and constant regions of immunoglobulin light chain precursors: implications on the organization and controlled expression of immunoglobulin genes. Biochemistry. 1978 Jun 13;17(12):2392–2400. doi: 10.1021/bi00605a022. [DOI] [PubMed] [Google Scholar]
  4. Edelman G. M., Gally J. A. Somatic recombination of duplicated genes: an hypothesis on the origin of antibody diversity. Proc Natl Acad Sci U S A. 1967 Feb;57(2):353–358. doi: 10.1073/pnas.57.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Farace M. G., Aellen M. F., Briand P. A., Faust C. H., Vassalli P., Mach B. No detectable reiteration of genes coding for mouse MOPC 41 immunoglobulin light-chain mRNA. Proc Natl Acad Sci U S A. 1976 Mar;73(3):727–731. doi: 10.1073/pnas.73.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Faust C. H., Diggelmann H., Mach B. Estimation of the number of genes coding for the constant part of the mouse immunoglobulin kappa light chain. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2491–2495. doi: 10.1073/pnas.71.6.2491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hamlyn P. H., Browniee G. G., Cheng C. C., Gait M. J., Milstein C. Complete sequence of constant and 3' noncoding regions of an immunoglobulin mRNA using the dideoxynucleotide method of RNA sequencing. Cell. 1978 Nov;15(3):1067–1075. doi: 10.1016/0092-8674(78)90290-8. [DOI] [PubMed] [Google Scholar]
  9. Honjo T., Packman S. Quantitation of constant and variable region genes for mouse immunoglobulin lambda chains. Biochemistry. 1976 Jun 29;15(13):2780–2785. doi: 10.1021/bi00658a012. [DOI] [PubMed] [Google Scholar]
  10. Honjo T., Packman S., Swan D., Nau M., Leder P. Organization of immunoglobulin genes: reiteration frequency of the mouse kappa chain constant region gene. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3659–3663. doi: 10.1073/pnas.71.9.3659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hood L., Campbell J. H., Elgin S. C. The organization, expression, and evolution of antibody genes and other multigene families. Annu Rev Genet. 1975;9:305–353. doi: 10.1146/annurev.ge.09.120175.001513. [DOI] [PubMed] [Google Scholar]
  12. Jeffreys A. J., Flavell R. A. A physical map of the DNA regions flanking the rabbit beta-globin gene. Cell. 1977 Oct;12(2):429–439. doi: 10.1016/0092-8674(77)90119-2. [DOI] [PubMed] [Google Scholar]
  13. Kabat E. A., Wu T. T., Bilofsky H. Evidence supporting somatic assembly of the DNA segments (minigenes), coding for the framework, and complementarity-determining segments of immunoglobulin variable regions. J Exp Med. 1979 Jun 1;149(6):1299–1313. doi: 10.1084/jem.149.6.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kabat E. A., Wu T. T., Bilofsky H. Variable region genes for the immunoglobulin framework are assembled from small segments of DNA--a hypothesis. Proc Natl Acad Sci U S A. 1978 May;75(5):2429–2433. doi: 10.1073/pnas.75.5.2429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leder P., Honjo T., Packman S., Swan D., Nau M., Norman B. The organization and diversity of immunoglobulin genes. Proc Natl Acad Sci U S A. 1974 Dec;71(12):5109–5115. doi: 10.1073/pnas.71.12.5109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  17. Marcu K. B., Valbuena O., Perry R. P. Isolation, purification, and properties of mouse heavy-chain immunoglobulin mRNAs. Biochemistry. 1978 May 2;17(9):1723–1733. doi: 10.1021/bi00602a022. [DOI] [PubMed] [Google Scholar]
  18. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  20. Rabbitts T. H., Jarvis J. M., Milstein C. Demonstration that a mouse immunoglobulin light chain messenger RNA hybridizes exclusively with unique DNA. Cell. 1975 Sep;6(1):5–12. doi: 10.1016/0092-8674(75)90067-7. [DOI] [PubMed] [Google Scholar]
  21. Rabbitts T. H., Milstein C. Mouse immunoglobulin genes: studies on the reiteration frequency of light-chain genes by hybridisation procedures. Eur J Biochem. 1975 Mar 3;52(1):125–133. doi: 10.1111/j.1432-1033.1975.tb03980.x. [DOI] [PubMed] [Google Scholar]
  22. Rudikoff S., Potter M. kappa Chain variable region from M167, a phosphorylcholine binding myeloma protein. Biochemistry. 1978 Jul 11;17(14):2703–2707. doi: 10.1021/bi00607a001. [DOI] [PubMed] [Google Scholar]
  23. SMITHIES O. GAMMA-GLOBULIN VARIABILITY: A GENETIC HYPOTHESIS. Nature. 1963 Sep 28;199:1231–1236. doi: 10.1038/1991231a0. [DOI] [PubMed] [Google Scholar]
  24. Seeburg P. H., Shine J., Martial J. A., Baxter J. D., Goodman H. M. Nucleotide sequence and amplification in bacteria of structural gene for rat growth hormone. Nature. 1977 Dec 8;270(5637):486–494. doi: 10.1038/270486a0. [DOI] [PubMed] [Google Scholar]
  25. Seidman J. G., Leder A., Edgell M. H., Polsky F., Tilghman S. M., Tiemeier D. C., Leder P. Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3881–3885. doi: 10.1073/pnas.75.8.3881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Seidman J. G., Leder A., Nau M., Norman B., Leder P. Antibody diversity. Science. 1978 Oct 6;202(4363):11–17. doi: 10.1126/science.99815. [DOI] [PubMed] [Google Scholar]
  27. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  28. Stavnezer J., Huang R. C., Stavnezer E., Bishop J. M. Isolation of messenger RNA for an immunoglobulin kappa chain and enumeration of the genes for the constatn region of kappa chain in the mouse. J Mol Biol. 1974 Sep 5;88(1):43–63. doi: 10.1016/0022-2836(74)90294-0. [DOI] [PubMed] [Google Scholar]
  29. Tabak H. F., Flavell R. A. A method for the recovery of DNA from agarose gels. Nucleic Acids Res. 1978 Jul;5(7):2321–2332. doi: 10.1093/nar/5.7.2321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tait R. C., Boyer H. W. Restriction endonuclease mapping of pSC101 and pMB9. Mol Gen Genet. 1978 Sep 8;164(3):285–288. doi: 10.1007/BF00333158. [DOI] [PubMed] [Google Scholar]
  31. Tonegawa S., Brack C., Hozumi N., Schuller R. Cloning of an immunoglobulin variable region gene from mouse embryo. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3518–3522. doi: 10.1073/pnas.74.8.3518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tonegawa S., Maxam A. M., Tizard R., Bernard O., Gilbert W. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1485–1489. doi: 10.1073/pnas.75.3.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tonegawa S. Reiteration frequency of immunoglobulin light chain genes: further evidence for somatic generation of antibody diversity. Proc Natl Acad Sci U S A. 1976 Jan;73(1):203–207. doi: 10.1073/pnas.73.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tonegawa S., Steinberg C., Dube S., Bernardini A. Evidence for somatic generation of antibody diversity. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4027–4031. doi: 10.1073/pnas.71.10.4027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Valbuena O., Marcu K. B., Weigert M., Perry R. P. Multiplicity of germline genes specifying a group of related mouse kappa chains with implications for the generation of immunoglobulin diversity. Nature. 1978 Dec 21;276(5690):780–784. doi: 10.1038/276780a0. [DOI] [PubMed] [Google Scholar]
  36. Villa-Komaroff L., Efstratiadis A., Broome S., Lomedico P., Tizard R., Naber S. P., Chick W. L., Gilbert W. A bacterial clone synthesizing proinsulin. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3727–3731. doi: 10.1073/pnas.75.8.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weigert M. G., Cesari I. M., Yonkovich S. J., Cohn M. Variability in the lambda light chain sequences of mouse antibody. Nature. 1970 Dec 12;228(5276):1045–1047. doi: 10.1038/2281045a0. [DOI] [PubMed] [Google Scholar]
  38. Wickens M. P., Buell G. N., Schimke R. T. Synthesis of double-stranded DNA complementary to lysozyme, ovomucoid, and ovalbumin mRNAs. Optimization for full length second strand synthesis by Escherichia coli DNA polymerase I. J Biol Chem. 1978 Apr 10;253(7):2483–2495. [PubMed] [Google Scholar]
  39. Witkin S. S., Korngold G. C., Bendich A. Ribonuclease-sensitive DNA-synthesizing complex in human sperm heads and seminal fluid. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3295–3299. doi: 10.1073/pnas.72.9.3295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES