Skip to main content
PMC home page
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
. 1981 Jun;78(6):3829–3833. doi: 10.1073/pnas.78.6.3829

Physical linkage of the constant region genes for immunoglobulins lambda I and lambda III.

J Miller, A Bothwell, U Storb
PMCID: PMC319666  PMID: 6267606

Abstract

During differentiation from a stem cell to an antibody-secreting cell, the immunoglobulin genes within a B cell undergo a rearrangement that juxtaposes a variable region gene to a constant region gene. To analyze the genetic organization of an immunoglobulin gene family in nonrearranged, germ-line DNA, we have constructed a recombinant DNA library from randomly cleaved mouse kidney DNA fragments. From this library, we have isolated three overlapping recombinant clones containing the constant region gene for lambda I light chains (C lambda I). These clones spanned 24.9 kilobases of mouse DNA and contained no variable region sequences. Hybridization of these clones with lambda II cDNA demonstrated the presence of an additional constant region gene and a joining region 3.2 kilobases 5' of C lambda I. This gene was tentatively identified as C lambda III by the absence of an Ava I endonuclease site, which is present within C lambda II. The C lambda III amino acid sequence has recently been reported [Azuma, T., Steiner, L. A. & Eisen, H. N. (1981) Proc. Natl. Acad. Sci. USA 78, 569-573] and is very closely related to the C lambda II amino acid sequence.

Full text

PDF
3832

Images in this article

3830Image
on p.3830
3831Image
on p.3831
3831Image
on p.3831
3832Image
on p.3832
3832Image
on p.3832

Selected References

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

  1. Appella E. Amino acid sequences of two mouse immunoglobulin lambda chains. Proc Natl Acad Sci U S A. 1971 Mar;68(3):590–594. doi: 10.1073/pnas.68.3.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azuma T., Steiner L. A., Eisen H. N. Identification of a third type of lambda light chain in mouse immunoglobulins. Proc Natl Acad Sci U S A. 1981 Jan;78(1):569–573. doi: 10.1073/pnas.78.1.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernard O., Hozumi N., Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978 Dec;15(4):1133–1144. doi: 10.1016/0092-8674(78)90041-7. [DOI] [PubMed] [Google Scholar]
  4. Blaser K., Eisen H. N. Lambda2 light chains in normal mouse immunoglobulins. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1495–1499. doi: 10.1073/pnas.75.3.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blattner F. R., Blechl A. E., Denniston-Thompson K., Faber H. E., Richards J. E., Slightom J. L., Tucker P. W., Smithies O. Cloning human fetal gamma globin and mouse alpha-type globin DNA: preparation and screening of shotgun collections. Science. 1978 Dec 22;202(4374):1279–1284. doi: 10.1126/science.725603. [DOI] [PubMed] [Google Scholar]
  6. Blattner F. R., Williams B. G., Blechl A. E., Denniston-Thompson K., Faber H. E., Furlong L., Grunwald D. J., Kiefer D. O., Moore D. D., Schumm J. W. Charon phages: safer derivatives of bacteriophage lambda for DNA cloning. Science. 1977 Apr 8;196(4286):161–169. doi: 10.1126/science.847462. [DOI] [PubMed] [Google Scholar]
  7. Bolivar F., Rodriguez R. L., Greene P. J., Betlach M. C., Heyneker H. L., Boyer H. W., Crosa J. H., Falkow S. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene. 1977;2(2):95–113. [PubMed] [Google Scholar]
  8. Bothwell A. L., Paskind M., Schwartz R. C., Sonenshein G. E., Gefter M. L., Baltimore D. Dual expression of lambda genes in the MOPC-315 plasmacytoma. Nature. 1981 Mar 5;290(5801):65–67. doi: 10.1038/290065a0. [DOI] [PubMed] [Google Scholar]
  9. Brack C., Hirama M., Lenhard-Schuller R., Tonegawa S. A complete immunoglobulin gene is created by somatic recombination. Cell. 1978 Sep;15(1):1–14. doi: 10.1016/0092-8674(78)90078-8. [DOI] [PubMed] [Google Scholar]
  10. Clarke L., Carbon J. A colony bank containing synthetic Col El hybrid plasmids representative of the entire E. coli genome. Cell. 1976 Sep;9(1):91–99. doi: 10.1016/0092-8674(76)90055-6. [DOI] [PubMed] [Google Scholar]
  11. Cotner T., Eisen H. N. The natural abundance of lambda2-light chains in inbred mice. J Exp Med. 1978 Nov 1;148(5):1388–1399. doi: 10.1084/jem.148.5.1388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. D'Eustachio P., Bothwell A. L., Takaro T. K., Baltimore D., Ruddle F. H. Chromosomal location of structural genes encoding murine immunoglobulin lambda light chains. Genetics of murine lambda light chains. J Exp Med. 1981 Apr 1;153(4):793–800. doi: 10.1084/jem.153.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dugan E. S., Bradshaw R. A., Simms E. S., Eisen H. N. Amino acid sequence of the light chain of a mouse myeloma protein (MOPC-315). Biochemistry. 1973 Dec 18;12(26):5400–5416. [PubMed] [Google Scholar]
  14. Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
  15. Fritsch E. F., Lawn R. M., Maniatis T. Molecular cloning and characterization of the human beta-like globin gene cluster. Cell. 1980 Apr;19(4):959–972. doi: 10.1016/0092-8674(80)90087-2. [DOI] [PubMed] [Google Scholar]
  16. Gottlieb P. D. Immunoglobulin genes. Mol Immunol. 1980 Nov;17(11):1423–1435. doi: 10.1016/0161-5890(80)90012-7. [DOI] [PubMed] [Google Scholar]
  17. Gough N. M., Cory S., Adams J. M. Identical 3' non-coding sequences in five mouse Ig kappa chain mRNAs favour a unique C kappa gene. Nature. 1979 Oct 4;281(5730):394–396. doi: 10.1038/281394a0. [DOI] [PubMed] [Google Scholar]
  18. Hieter P. A., Max E. E., Seidman J. G., Maizel J. V., Jr, Leder P. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments. Cell. 1980 Nov;22(1 Pt 1):197–207. doi: 10.1016/0092-8674(80)90168-3. [DOI] [PubMed] [Google Scholar]
  19. Lacy E., Hardison R. C., Quon D., Maniatis T. The linkage arrangement of four rabbit beta-like globin genes. Cell. 1979 Dec;18(4):1273–1283. doi: 10.1016/0092-8674(79)90238-1. [DOI] [PubMed] [Google Scholar]
  20. Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [DOI] [PubMed] [Google Scholar]
  21. Liu C. P., Tucker P. W., Mushinski J. F., Blattner F. R. Mapping of heavy chain genes for mouse immunoglobulins M and D. Science. 1980 Sep 19;209(4463):1348–1353. doi: 10.1126/science.6774414. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Maniatis T., Jeffrey A., van deSande H. Chain length determination of small double- and single-stranded DNA molecules by polyacrylamide gel electrophoresis. Biochemistry. 1975 Aug 26;14(17):3787–3794. doi: 10.1021/bi00688a010. [DOI] [PubMed] [Google Scholar]
  24. Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  26. Newell N., Richards J. E., Tucker P. W., Blattner F. R. J genes for heavy chain immunoglobulins of mouse. Science. 1980 Sep 5;209(4461):1128–1132. doi: 10.1126/science.6250219. [DOI] [PubMed] [Google Scholar]
  27. Parker R. C., Seed B. Two-dimensional agarose gel electrophoresis "SeaPlaque" agarose dimension. Methods Enzymol. 1980;65(1):358–363. [PubMed] [Google Scholar]
  28. Proudfoot N. J., Maniatis T. The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene duplication. Cell. 1980 Sep;21(2):537–544. doi: 10.1016/0092-8674(80)90491-2. [DOI] [PubMed] [Google Scholar]
  29. Schwarz E., Scherer G., Hobom G., Kössel H. Nucleotide sequence of cro, cII and part of the O gene in phage lambda DNA. Nature. 1978 Mar 30;272(5652):410–414. doi: 10.1038/272410a0. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Selsing E., Wells R. D. Preparation of triple-block DNA polymers using recombinant DNA techniques. Nucleic Acids Res. 1979 Jul 11;6(9):3025–3040. doi: 10.1093/nar/6.9.3025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Sugino A., Goodman H. M., Heyneker H. L., Shine J., Boyer H. W., Cozzarelli N. R. Interaction of bacteriophage T4 RNA and DNA ligases in joining of duplex DNA at base-paired ends. J Biol Chem. 1977 Jun 10;252(11):3987–3994. [PubMed] [Google Scholar]
  34. 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]
  35. Walfield A. M., Storb U., Selsing E., Zentgraf H. Comparison of different rearranged immunoglobulin kappa genes of a myeloma by electronmicroscopy and restriction mapping of cloned DNA: implications for "allelic exclusion". Nucleic Acids Res. 1980 Oct 24;8(20):4689–4707. doi: 10.1093/nar/8.20.4689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weigert M., Riblet R. Genetic control of antibody variable regions. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):837–846. doi: 10.1101/sqb.1977.041.01.093. [DOI] [PubMed] [Google Scholar]
  37. Wilson R., Miller J., Storb U. Rearrangement of immunoglobulin genes. Biochemistry. 1979 Oct 30;18(22):5013–5021. doi: 10.1021/bi00589a032. [DOI] [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