Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1989 Jul;77(1):130–136.

Expression and sequences of T cell receptor beta-chain variable genes in the enlarged lymph nodes of C57BL/6-lpr/lpr mice.

S Ohga 1, Y Yoshikai 1, K Kishihara 1, G Matsuzaki 1, T Asano 1, K Nomoto 1
PMCID: PMC1541919  PMID: 2548776

Abstract

An autosomal recessive gene, lpr, is responsible for lymphoproliferation and autoimmunity of lpr-mice, in which background genes are also known to influence the development of autoimmune disease. To define the differences in abnormally proliferating T cells between C57BL/6-lpr/lpr and MRL/Mp-lpr/lpr mice, and to try and understand the influence of background in the differing expression of autoimmune disease in both strains, we analysed the sequences of T cell antigen receptor V beta genes expressed in the cells from the enlarged lymph nodes of C57BL/6-lpr/lpr mice. Eleven beta cDNAs out of the 38 C beta-specific cDNAs contained sequences with open reading frames from the beginning of the variable region to the expected termination codons at the end of the constant regions. Notably, 36% of the functional beta-chain mRNAs expressed V beta 8.3 genes, whereas V beta 8.1 and V beta 8.2 genes were not found. These results are consistent with a relatively lower frequency of the V beta 8.1 or V beta 8.2 expressing cells in the hypertrophic lymph nodes of C57BL/6-lpr/lpr mice, detected by KJ16-133 monoclonal antibody. Interestingly, other V beta genes expressed in these mice were completely distinct from those in MRL/Mp-lpr/lpr mice as described by Singer et al. (1986). The different distribution of V beta genes expressed in C57BL/6-lpr/lpr from that in MRL/Mp-lpr/lpr mice might be related to the differences in the genetic background and the expression of lpr gene-associated autoimmunity.

Full text

PDF
132

Images in this article

132Fig. 1
on p.132

Selected References

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

  1. Allison J. P., Lanier L. L. Structure, function, and serology of the T-cell antigen receptor complex. Annu Rev Immunol. 1987;5:503–540. doi: 10.1146/annurev.iy.05.040187.002443. [DOI] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
  4. Behlke M. A., Henkel T. J., Anderson S. J., Lan N. C., Hood L., Braciale V. L., Braciale T. J., Loh D. Y. Expression of a murine polyclonal T cell receptor marker correlates with the use of specific members of the V beta 8 gene segment subfamily. J Exp Med. 1987 Jan 1;165(1):257–262. doi: 10.1084/jem.165.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Behlke M. A., Spinella D. G., Chou H. S., Sha W., Hartl D. L., Loh D. Y. T-cell receptor beta-chain expression: dependence on relatively few variable region genes. Science. 1985 Aug 9;229(4713):566–570. doi: 10.1126/science.3875151. [DOI] [PubMed] [Google Scholar]
  6. Budd R. C., Cerottini J. C., MacDonald H. R. Cultured Lyt-2- L3T4- T lymphocytes from normal thymus or lpr mice express a broad spectrum of cytolytic activity. J Immunol. 1986 Dec 15;137(12):3734–3741. [PubMed] [Google Scholar]
  7. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Clark D. A., Cinader B., Rosenthal K. L., Koh S. Y., Chaput A. Strain-dependence and cellular aspects of the acceleration of age-dependent shift in class-specific helper and suppressor activity in the thymus of MRL/Mp mice by the LPR gene. Cell Immunol. 1985 Dec;96(2):418–429. doi: 10.1016/0008-8749(85)90372-7. [DOI] [PubMed] [Google Scholar]
  10. Crispe I. N., Moore M. W., Husmann L. A., Smith L., Bevan M. J., Shimonkevitz R. P. Differentiation potential of subsets of CD4-8- thymocytes. Nature. 1987 Sep 24;329(6137):336–339. doi: 10.1038/329336a0. [DOI] [PubMed] [Google Scholar]
  11. Fowlkes B. J., Kruisbeek A. M., Ton-That H., Weston M. A., Coligan J. E., Schwartz R. H., Pardoll D. M. A novel population of T-cell receptor alpha beta-bearing thymocytes which predominantly expresses a single V beta gene family. Nature. 1987 Sep 17;329(6136):251–254. doi: 10.1038/329251a0. [DOI] [PubMed] [Google Scholar]
  12. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  13. Hashimoto Y., Maxam A. M., Greene M. I. T-cell antigen-receptor genes in autoimmune mice. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7865–7869. doi: 10.1073/pnas.83.20.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hashimoto Y., Yui K., Littman D., Greene M. I. T-cell receptor genes in autoimmune mice: T-cell subsets have unexpected T-cell receptor gene programs. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5883–5887. doi: 10.1073/pnas.84.16.5883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  16. Izui S., Kelley V. E., Masuda K., Yoshida H., Roths J. B., Murphy E. D. Induction of various autoantibodies by mutant gene lpr in several strains of mice. J Immunol. 1984 Jul;133(1):227–233. [PubMed] [Google Scholar]
  17. Kelley V. E., Roths J. B. Interaction of mutant lpr gene with background strain influences renal disease. Clin Immunol Immunopathol. 1985 Nov;37(2):220–229. doi: 10.1016/0090-1229(85)90153-9. [DOI] [PubMed] [Google Scholar]
  18. Kishihara K., Yoshikai Y., Matsuzaki G., Mak T. W., Nomoto K. Functional alpha and beta T cell chain receptor messages can be detected in old but not in young athymic mice. Eur J Immunol. 1987 Apr;17(4):477–482. doi: 10.1002/eji.1830170407. [DOI] [PubMed] [Google Scholar]
  19. MacDonald H. R., Howe R. C., Pedrazzini T., Lees R. K., Budd R. C., Schneider R., Liao N. S., Zinkernagel R. M., Louis J. A., Raulet D. H. T-cell lineages, repertoire selection and tolerance induction. Immunol Rev. 1988 Aug;104:157–182. doi: 10.1111/j.1600-065x.1988.tb00762.x. [DOI] [PubMed] [Google Scholar]
  20. Nemazee D. A., Studer S., Steinmetz M., Dembić Z., Kiefer M. The lymphoproliferating cells of MRL-lpr/lpr mice are a polyclonal population that bear the T lymphocyte receptor for antigen. Eur J Immunol. 1985 Aug;15(8):760–764. doi: 10.1002/eji.1830150804. [DOI] [PubMed] [Google Scholar]
  21. Santoro T. J., Lehmann K. R., Batt R. A., Kotzin B. L. The role of L3T4+ cells in the pathogenesis of lupus in lpr-bearing mice. I. Defects in the production of interleukins 2 and 3. Eur J Immunol. 1987 Aug;17(8):1131–1136. doi: 10.1002/eji.1830170809. [DOI] [PubMed] [Google Scholar]
  22. Singer P. A., McEvilly R. J., Noonan D. J., Dixon F. J., Theofilopoulos A. N. Clonal diversity and T-cell receptor beta-chain variable gene expression in enlarged lymph nodes of MRL-lpr/lpr lupus mice. Proc Natl Acad Sci U S A. 1986 Sep;83(18):7018–7022. doi: 10.1073/pnas.83.18.7018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Snodgrass H. R., Kisielow P., Kiefer M., Steinmetz M., von Boehmer H. Ontogeny of the T-cell antigen receptor within the thymus. Nature. 1985 Feb 14;313(6003):592–595. doi: 10.1038/313592a0. [DOI] [PubMed] [Google Scholar]
  24. Theofilopoulos A. N., Balderas R. S., Shawler D. L., Lee S., Dixon F. J. Influence of thymic genotype on the systemic lupus erythematosus-like disease and T cell proliferation of MRL/Mp-lpr/lpr mice. J Exp Med. 1981 Jun 1;153(6):1405–1414. doi: 10.1084/jem.153.6.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Theofilopoulos A. N., Dixon F. J. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390. doi: 10.1016/s0065-2776(08)60342-9. [DOI] [PubMed] [Google Scholar]
  26. Wilson R. K., Lai E., Concannon P., Barth R. K., Hood L. E. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. doi: 10.1111/j.1600-065x.1988.tb00736.x. [DOI] [PubMed] [Google Scholar]
  27. Wofsy D., Murphy E. D., Roths J. B., Dauphinée M. J., Kipper S. B., Talal N. Deficient interleukin 2 activity in MRL/Mp and C57BL/6J mice bearing the lpr gene. J Exp Med. 1981 Nov 1;154(5):1671–1680. doi: 10.1084/jem.154.5.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yoshida H., Yoshida M., Izui S., Lambert P. H. Distinct clonotypes of anti-DNA antibodies in mice with lupus nephritis. J Clin Invest. 1985 Aug;76(2):685–694. doi: 10.1172/JCI112022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. von Boehmer H. The developmental biology of T lymphocytes. Annu Rev Immunol. 1988;6:309–326. doi: 10.1146/annurev.iy.06.040188.001521. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES