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. 1981 Jul 1;154(1):146–155. doi: 10.1084/jem.154.1.146

Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus

PMCID: PMC2186393  PMID: 6788891

Abstract

We previously showed that a chromosome 6 locus, IgK-Ef2, controls a pair of prominent bands in normal mouse light-chain isoelectric focusing profiles. Screening of myeloma light chains derived from BALB/c mice (an IgK-EF2 alpha strain) led to the identification of seven light chains cofocusing with the polymorphic bands controlled by IgK-Ef2. Complete sequencing of the variable (V) regions of four of the light chains indicates that they are all members of the same subgroup (Vk-1A) and they differ from one another by 1--3 substitutions. One of the protein differs from the prototype V-region sequence only in the deletion of a single residue at position 95 immediately preceding of J region. The other two differ from the protype V region by 3 (two framework [fr], one complementarity-determined [cdr]) and one (fr) residues, respectively. Complete V-region sequences of two closely related light chains derived from NZB mice (an IgK-Ef2b strain) indicate the NZB proteins are derived from a distinct Vk gene (Vk-1B), differing by four substitutions from the Vk-1A sequence. The results suggest that the IgK-Ef2 polymorphism may be a result of, at least in part, the loss of the gene(s) coding for the Vk-1A subgroups in IgK- Ef2b strains of mice. The nature of the sequence diversity found in the Vk-1A subgroup indicates that either it is coded by a repeated series of virtually identical genes or that somatic mutation of a single Vk-1A gene may give rise to substitutions in framework as well as cdr regions.

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Selected References

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

  1. 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]
  2. Drapeau G. R. Cleavage at glutamic acid with staphylococcal protease. Methods Enzymol. 1977;47:189–191. doi: 10.1016/0076-6879(77)47023-x. [DOI] [PubMed] [Google Scholar]
  3. Franek F., Brummelová V., Skvaril F. Isolation and characterization of kappa and lambda chains of normal human gammaG-immunoglobulin. Biochim Biophys Acta. 1968 Aug 13;160(3):321–332. doi: 10.1016/0005-2795(68)90205-5. [DOI] [PubMed] [Google Scholar]
  4. Gibson D. M., MacLean S. J. Ef2: a new LY-3-linked light-chain marker expressed in normal mouse serum immunoglobulin. J Exp Med. 1979 Jun 1;149(6):1477–1486. doi: 10.1084/jem.149.6.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gibson D. M., Taylor B. A., Cherry M. Evidence for close linkage of a mouse light chain marker with the Ly-2,3 locus. J Immunol. 1978 Oct;121(4):1585–1590. [PubMed] [Google Scholar]
  6. Gibson D. Genetic polymorphism of mouse immunoglobulin light chains revealed by isoelectric focusing. J Exp Med. 1976 Jul 1;144(1):298–303. doi: 10.1084/jem.144.1.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gottlieb P. D., Tsang H. C., Gibson D. M., Cannon L. E. Unique V kappa group associated with two mouse L chain genetic markers. Proc Natl Acad Sci U S A. 1981 Jan;78(1):559–563. doi: 10.1073/pnas.78.1.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hengartner H., Meo T., Müller E. Assignment of genes for immunoglobulin kappa and heavy chains to chromosomes 6 and 12 in mouse. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4494–4498. doi: 10.1073/pnas.75.9.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hood L., Loh E., Hubert J., Barstad P., Eaton B., Early P., Fuhrman J., Johnson N., Kronenberg M., Schilling J. The structure and genetics of mouse immunoglobulins: an analysis of NZB myeloma proteins and sets of BALB/c myeloma proteins binding particular haptens. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):817–836. doi: 10.1101/sqb.1977.041.01.092. [DOI] [PubMed] [Google Scholar]
  10. Hunkapiller M. W., Hood L. E. Direct microsequence analysis of polypeptides using an improved sequenator, a nonprotein carrier (polybrene), and high pressure liquid chromatography. Biochemistry. 1978 May 30;17(11):2124–2133. doi: 10.1021/bi00604a016. [DOI] [PubMed] [Google Scholar]
  11. Jaffe B. M., Eisen H. N., Simms E. S., Potter M. Myeloma proteins with anti-hapten antibody activity: epsilon-2,4-dinitrophenyl lysine binding by the protein produced by mouse plasmacytoma MOPC-460. J Immunol. 1969 Oct;103(4):872–874. [PubMed] [Google Scholar]
  12. Johnson N. D., Hunkapiller M. W., Hood L. E. Analysis of phenylthiohydantoin amino acids by high-performance liquid chromatography on DuPont Zobax cyanopropylsilane columns. Anal Biochem. 1979 Dec;100(2):335–338. doi: 10.1016/0003-2697(79)90237-9. [DOI] [PubMed] [Google Scholar]
  13. Johnson P., Stockmal V. B. o-Iodosobenzoic acid: peptide bond cleavage at tyrosine in addition to tryptophan residues. Biochem Biophys Res Commun. 1980 May 30;94(2):697–703. doi: 10.1016/0006-291x(80)91288-7. [DOI] [PubMed] [Google Scholar]
  14. Lazure C., Hum W. T., Gibson D. M. A major group of mouse kappa chains controlled by the chromosome 6 locus, IgK-Ef2. J Exp Med. 1980 Sep 1;152(3):555–564. doi: 10.1084/jem.152.3.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Loh E., Black B., Riblet R., Weigert M., Hood J. M., Hood L. Myeloma proteins from NZB and BALB/c mice: structural and functional differences. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1395–1399. doi: 10.1073/pnas.76.3.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mahoney W. C., Hermodson M. A. High-yield cleavage of tryptophanyl peptide bonds by o-iodosobenzoic acid. Biochemistry. 1979 Aug 21;18(17):3810–3814. doi: 10.1021/bi00584a026. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Max E. E., Seidman J. G., Miller H., Leder P. Variation in the crossover point of kappa immunoglobulin gene V-J recombination: evidence from a cryptic gene. Cell. 1980 Oct;21(3):793–799. doi: 10.1016/0092-8674(80)90442-0. [DOI] [PubMed] [Google Scholar]
  19. McKean D. J., Bell M., Potter M. Mechanisms of antibody diversity: multiple genes encode structurally related mouse kappa variable regions. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3913–3917. doi: 10.1073/pnas.75.8.3913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Potter M. Antigen-binding myeloma proteins of mice. Adv Immunol. 1977;25:141–211. [PubMed] [Google Scholar]
  21. Potter M. Immunoglobulin-producing tumors and myeloma proteins of mice. Physiol Rev. 1972 Jul;52(3):631–719. doi: 10.1152/physrev.1972.52.3.631. [DOI] [PubMed] [Google Scholar]
  22. Rudikoff S., Rao D. N., Glaudemans C. P., Potter M. kappa Chain joining segments and structural diversity of antibody combining sites. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4270–4274. doi: 10.1073/pnas.77.7.4270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Smithies O., Gibson D., Fanning E. M., Goodfliesh R. M., Gilman J. G., Ballantyne D. L. Quantitative procedures for use with the Edman-Begg sequenator. Partial sequences of two unusual immunoglobulin light chains, Rzf and Sac. Biochemistry. 1971 Dec 21;10(26):4912–4921. doi: 10.1021/bi00802a013. [DOI] [PubMed] [Google Scholar]
  26. Swan D., D'Eustachio P., Leinwand L., Seidman J., Keithley D., Ruddle F. H. Chromosomal assignment of the mouse kappa light chain genes. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2735–2739. doi: 10.1073/pnas.76.6.2735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. WEIGERT M. G., GAREN A. AMINO ACID SUBSTITUTIONS RESULTING FROM SUPPRESSION OF NONSENSE MUTATIONS. I. SERINE INSERTION BY THE SU-1 SUPPRESSOR GENE. J Mol Biol. 1965 Jun;12:448–455. doi: 10.1016/s0022-2836(65)80267-4. [DOI] [PubMed] [Google Scholar]
  29. Weigert M., Gatmaitan L., Loh E., Schilling J., Hood L. Rearrangement of genetic information may produce immunoglobulin diversity. Nature. 1978 Dec 21;276(5690):785–790. doi: 10.1038/276785a0. [DOI] [PubMed] [Google Scholar]
  30. Weigert M., Perry R., Kelley D., Hunkapiller T., Schilling J., Hood L. The joining of V and J gene segments creates antibody diversity. Nature. 1980 Jan 31;283(5746):497–499. doi: 10.1038/283497a0. [DOI] [PubMed] [Google Scholar]

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