Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Mar 1;173(3):629–637. doi: 10.1084/jem.173.3.629

An isotype-specific trans-acting factor is defective in a mutant B cell line that expresses HLA-DQ, but not -DR or -DP

PMCID: PMC2118821  PMID: 1997650

Abstract

The B lymphoblastoid cell line clone 13 (a subclone of the mutant cell line P3JHR-1) has been found to express high levels of HLA-DQ; by contrast, HLA-DR and -DP antigens are not expressed and cannot be induced by interferon gamma. Northern blot analysis using gene-specific probes indicated that the lack of surface expression of the DR and DP antigens is due to a marked decrease in the levels of steady-state RNA for both the alpha and beta chains. Southern blots demonstrated that none of the transcriptionally repressed genes are grossly deleted. Preparations of interspecific transient heterokaryons between clone 13 and the class II antigen-positive murine B cell lymphoma, A20, resulted in reactivation of the DRA gene and surface expression of both the DR and DP molecules. The efficiency of the DRA promoter relative to the DQB promoter is markedly and specifically diminished in clone 13 (P3JHR- 1) as compared with the parental cell line, Jijoye, as assayed both by transient expression of appropriate chloramphenicol acetyltransferase gene (CAT) constructs and by in vitro transcription analysis. These data clearly demonstrate the existence of an isotype-specific trans- acting factor, and provide direct evidence that the highly homologous class II genes have distinct regulatory mechanisms.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Accolla R. S. Human B cell variants immunoselected against a single Ia antigen subset have lost expression of several Ia antigen subsets. J Exp Med. 1983 Mar 1;157(3):1053–1058. doi: 10.1084/jem.157.3.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anichini A., Castelli C., Sozzi G., Fossati G., Parmiani G. Differential susceptibility to recombinant interferon-gamma-induced HLA-DQ antigen modulation among clones from a human metastatic melanoma. J Immunol. 1988 Jan 1;140(1):183–191. [PubMed] [Google Scholar]
  3. Basta P. V., Sherman P. A., Ting J. P. Identification of an interferon-gamma response region 5' of the human histocompatibility leukocyte antigen DR alpha chain gene which is active in human glioblastoma multiforme lines. J Immunol. 1987 Feb 15;138(4):1275–1280. [PubMed] [Google Scholar]
  4. Benacerraf B. Role of MHC gene products in immune regulation. Science. 1981 Jun 12;212(4500):1229–1238. doi: 10.1126/science.6165083. [DOI] [PubMed] [Google Scholar]
  5. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  6. Blanck G., Lok M., Kok K., Downie E., Korn J. H., Strominger J. L. Gamma-interferon induction of HLA class II mRNAs in dermal fibroblasts studied by RNAse protection analysis. Hum Immunol. 1990 Oct;29(2):150–156. doi: 10.1016/0198-8859(90)90078-4. [DOI] [PubMed] [Google Scholar]
  7. Boothby M., Liou H. C., Glimcher L. H. Differences in DNA sequence specificity among MHC class II X box binding proteins. J Immunol. 1989 Feb 1;142(3):1005–1014. [PubMed] [Google Scholar]
  8. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  9. Celada A., Maki R. A. DNA binding of the mouse class II major histocompatibility CCAAT factor depends on two components. Mol Cell Biol. 1989 Jul;9(7):3097–3100. doi: 10.1128/mcb.9.7.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cooper M. D., Bucy R. P., George J. F., Lahti J. M., Char D., Chen C. L. T-cell development in birds. Cold Spring Harb Symp Quant Biol. 1989;54(Pt 1):69–73. doi: 10.1101/sqb.1989.054.01.009. [DOI] [PubMed] [Google Scholar]
  11. Heston L., Rabson M., Brown N., Miller G. New Epstein-Barr virus variants from cellular subclones of P3J-HR-1 Burkitt lymphoma. Nature. 1982 Jan 14;295(5845):160–163. doi: 10.1038/295160a0. [DOI] [PubMed] [Google Scholar]
  12. Hinuma Y., Konn M., Yamaguchi J., Wudarski D. J., Blakeslee J. R., Jr, Grace J. T., Jr Immunofluorescence and herpes-type virus particles in the P3HR-1 Burkitt lymphoma cell line. J Virol. 1967 Oct;1(5):1045–1051. doi: 10.1128/jvi.1.5.1045-1051.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hume C. R., Lee J. S. Congenital immunodeficiencies associated with absence of HLA class II antigens on lymphocytes result from distinct mutations in trans-acting factors. Hum Immunol. 1989 Dec;26(4):288–309. doi: 10.1016/0198-8859(89)90007-4. [DOI] [PubMed] [Google Scholar]
  14. Hume C. R., Shookster L. A., Collins N., O'Reilly R., Lee J. S. Bare lymphocyte syndrome: altered HLA class II expression in B cell lines derived from two patients. Hum Immunol. 1989 May;25(1):1–11. doi: 10.1016/0198-8859(89)90065-7. [DOI] [PubMed] [Google Scholar]
  15. Marcadet A., Cohen D., Dausset J., Fischer A., Durandy A., Griscelli C. Genotyping with DNA probes in combined immunodeficiency syndrome with defective expression of HLA. N Engl J Med. 1985 May 16;312(20):1287–1292. doi: 10.1056/NEJM198505163122004. [DOI] [PubMed] [Google Scholar]
  16. Miwa K., Strominger J. L. The HLA-DQ beta gene upstream region contains an immunoglobulin-like octamer motif that binds cell-type specific nuclear factors. Nucleic Acids Res. 1987 Oct 12;15(19):8057–8067. doi: 10.1093/nar/15.19.8057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Okada K., Boss J. M., Prentice H., Spies T., Mengler R., Auffray C., Lillie J., Grossberger D., Strominger J. L. Gene organization of DC and DX subregions of the human major histocompatibility complex. Proc Natl Acad Sci U S A. 1985 May;82(10):3410–3414. doi: 10.1073/pnas.82.10.3410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pujol-Borrell R., Todd I., Doshi M., Bottazzo G. F., Sutton R., Gray D., Adolf G. R., Feldmann M. HLA class II induction in human islet cells by interferon-gamma plus tumour necrosis factor or lymphotoxin. Nature. 1987 Mar 19;326(6110):304–306. doi: 10.1038/326304a0. [DOI] [PubMed] [Google Scholar]
  19. Saito H., Maki R. A., Clayton L. K., Tonegawa S. Complete primary structures of the E beta chain and gene of the mouse major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5520–5524. doi: 10.1073/pnas.80.18.5520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sakurai M., Strominger J. L. Studies of expression of the DQ beta promoter and its 5' deletion derivatives in normal and mutant human B cell lines. Tissue Antigens. 1989 Jul;34(1):64–77. doi: 10.1111/j.1399-0039.1989.tb01718.x. [DOI] [PubMed] [Google Scholar]
  21. Symington F. W., Levine F., Braun M., Brown S. L., Erlich H. A., Torok-Storb B. Differential Ia antigen expression by autologous human erythroid and B lymphoblastoid cell lines. J Immunol. 1985 Aug;135(2):1026–1032. [PubMed] [Google Scholar]
  22. Yang Z., Accolla R. S., Pious D., Zegers B. J., Strominger J. L. Two distinct genetic loci regulating class II gene expression are defective in human mutant and patient cell lines. EMBO J. 1988 Jul;7(7):1965–1972. doi: 10.1002/j.1460-2075.1988.tb03034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. de Préval C., Hadam M. R., Mach B. Regulation of genes for HLA class II antigens in cell lines from patients with severe combined immunodeficiency. N Engl J Med. 1988 May 19;318(20):1295–1300. doi: 10.1056/NEJM198805193182003. [DOI] [PubMed] [Google Scholar]
  24. de Préval C., Lisowska-Grospierre B., Loche M., Griscelli C., Mach B. A trans-acting class II regulatory gene unlinked to the MHC controls expression of HLA class II genes. Nature. 1985 Nov 21;318(6043):291–293. doi: 10.1038/318291a0. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES