Abstract
The major transplantation (or H-2) antigens in the mouse are cell-surface glycoproteins composed of a heavy chain and a light chain, the beta-2 microglobulin (β 2m). The expression of these proteins is regulated during development. Embryonic cells at early stages of development do not express these proteins. On the other hand, these molecules are present on the surface of all adult somatic cells. We investigated whether the expression of both chains was coordinately regulated. Using specific single-stranded DNA probes in an S1 nuclease analysis, we compared the relative amounts of H-21) and β 2M transcripts in normal tissues, in transformed cells, and during embryonic development. Our results show that (1) the steady state level of β 2m transcripts varies from one adult organ to another, while that of H-2D transcripts stays approximately the same; (2) upon transformation, the amount of H-2D-specific mRNA increases drastically, while the β 2m mRNA level remains constant; (3) whereas the quantity of β 2m mRNA increases during early development, the amount of H-2D mRNA remains at a very low level. These data suggest that the regulation of H-2D and β 2m genes are not identical and that their activation during development is not synchronous.
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Auffray, C. and Rougeon, F.: Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur. J. Biochem. 107: 303–314, 1980
Brickell, P. M., Latchman, D. S., Murphy, D., Willison, K., and Rigby, P. W. J.: Activation of a Qa/Tla class I major histocompatibility antigen gene is a general feature of oncogenesis in the mouse. Nature 306: 756–760, 1983
Buc-Caron, M. H., Condamine, H., and Jacob, F.: The presence of F9 antigen on the surface of mouse embryonic cells until day 8 of embryogenesis. J. Embryol. Exp. Morphol. 47: 149–160, 1978
Cami, B., Bregegere, F., Abastado, J. P., and Kourilsky, P.: Multiple sequences related to classical histocompatibility antigens in the mouse. Nature 291: 673–675, 1981
Clegg, K. B. and Piko, L.: Poly(A) length, cytoplasmic adenylation and synthesis of poly(A)+ RNA in early mouse embryos. Dev. Biol. 95: 331–341, 1983
Croce, C. M., Linnenbach, A., Huebner, K., Parnes, J. R., Margulies, D. H., Appella, E., and Seidman, J. G.: Control of expression of histocompatibility antigens (H-2) and β2-microglobulin in F9 teratocarcinoma stem cells. Proc. Natl. Acad. Sci. U.S.A. 78: 5754–5758, 1981
Daniel, F., Morello, D., Lebail, O., Chambon, P., Cayre, Y., and Kourilsky, P.: Structure and expression of the mouse β 2- microglobulin gene isolated from somatic and non expressing teratocarcinoma cells. EMBO J. 2: 1060–1065, 1983
Fellous, M., Kamoun, M., Wiels, J., Dausset, J., Clements, G., Zeuthen, J., and Klein, G.: Induction of HLA expression in Daudi cells after cell fusion. Immunogenetics 5: 423–436, 1977
Gates, F. T., Coligan, J. E., and Kindt, T. J.: Complete amino acid sequence of murine β 2-microglobulin: Structural evidence for strain-related polymorphism. Proc. Natl. Acad. Sci. U.S.A. 77: 7395–7399, 1981
Geib, R., Poulik, M. D., Vitetta, E. S., Kearney, J. F., and Klein, J.: Relationship between β2-microglobulin and cell-surface alloantigens of the mouse. J. Immunol. 117: 1532–1537, 1976
Hyman, R. and Stallings, V.: Analysis of hybrids between an H-2+, TL− lymphoma and an H-2+, TL′ lymphoma and its H-2−, TL− variant subline. Immunogenetics 4: 171–181, 1977
Kelly, F.: Chromosome analysis of a SV40 transformed cell line and two variant sublines that are resistant to cytochalasin B. Cancer Res. 35: 1210–1213, 1975
Klein, J.: The major histocompatibility complex of the mouse. Science 203: 516–521, 1979
Kress, M., Liu, W.-Y., Jay, E., Khoury, G., and Jay, G.: Comparison of class I (H-2) gene sequences. J. Biol. Chem. 258: 13 929–13 935, 1983
Kress, M., Barra, Y., Seidman, J. G., Khoury, G., and Jay, G.: Functional insertion of an Alu type 2 (B2 SINE) repetitive sequence in murine class I genes. Science 226: 974–982, 1984
Lalanne, J. L., Bregegere, F., Delarbre, C., Abastado, J. P., Gachelin, G., and Kourilsky, P.: Comparison of nucleotide sequences of mRNAs belonging to the mouse H-2 multigene family. Nucleic Acids Res. 10: 1039–1049, 1982
Lalanne, J. L., Transy, C., Guerin, S., Darche, S., Meulien, P., and Kourilsky, P.: Expression of class I genes in the major histocompatibility complex: Identification of eight distinct mRNAs in DBA/2 mouse liver. Cell 41: 469–478, 1985
Melnick, M., Jaskoll, T., and Marazita, M.: Localization of H-2Kk in developing mouse palates using monoclonal antibodies. J. Embryol. Exp. Morphol. 70: 45–60, 1982
Morello, D., Gachelin, G., Dubois, P., Tanigaki, N., Pressman, D., and Jacob, F.: Absence of reaction of a xenogenic anti H-2 serum with mouse embryonal carcinoma cells. Transplantation 26: 119–125, 1978
Morello, D., Daniel, F., Baldacci, P., Cayre, Y., Gachelin, G., and Kourilsky, P.: Absence of significant H-2 and β2-microglobulin mRNA expression by mouse embryonal carcinoma cells. Nature 296: 260–262, 1982
Murphy, D., Brickell, P. M., Latchman, D. S., Willison, K., and Rigby, P. W. J.: Transcripts regulated during normal embryonic development and oncogenic transformation share a repetitive element. Cell 35: 865–871, 1983
Nicolas, J. F. and Berg, P.: Regulation of expression of genes transduced into embryonal carcinoma cells. Cold Spring Harbor Conf. Cell Prolif. 10: 469–485, 1983
Nicolas, J. F., Jakob, H., and Jacob, F.: Teratocarcinoma derived cell lines and their use in the study of differentiation. In G. Sato (ed.): Functionally Differentiated Cell Lines, pp. 185–210, Alan R. Liss Inc., New York, 1981
Ostrand-Rosenberg, S.: Cell mediated immune responses to mouse embryonic cells: Detection and characterization of embryonic antigens. Curr. Top. Dev. Biol. 14: 147–168, 1980
Ozato, K., Wan, Y. J., and Orrison, B. M.: Mouse major histocompatibility class I gene expression begins at midsomite and is inducible in earlier-stage embryos by interferon. Proc. Natl. Acad. Sci. U.S.A. 82: 2427–2431,1985
Parnes, J. R. and Seidman, J. G.: Structure of wild-type and mutant mouse β 2-microglobulin genes. Cell 29: 661–669, 1982
Parries, J. R., Velan, B., Felsenfeld, A., Ramanathan, L., Ferrini, U., Appella, E. and Seidman, J. G.: Mouse β 2-microglobulin cDNA clones: A screening procedure for cDNA clones corresponding to rare mRNAs. Proc. Natl. Acad. Sci. U.S.A. 78: 2253–2257, 1981
Ploegh, H. L., Orr, H. T., and Strominger, J. L.: Major histocompatibility antigens: The human (HLA-A, -B, -C) and murine (H-2K, H-2D) class I molecules. Cell 24: 287–291, 1981
Potter, T. A., Boyer, C., Schmitt-Verhulst, A. M., Golstein, P., and Rajan, T. V.: Expression of H-2Db on the cell surface in the absence of detectable β 2-microglobulin. J. Exp. Med. 160: 317–322, 1984
Potter, T. A., Zeff, R. A., Schmitt-Verhulst, A. M., and Rajan, T. V.: Molecular analysis of an EL4 cell line that expresses H-2Db but not H-2Kb or β 2 microglobulin. Proc. Natl. Acad. Sci. U.S.A. 82: 2950–2954, 1985
Rosenthal, A., Wright, S., Cedar, H., Flavell, R., and Grosveld, F.: Regulated expression of an introduced MHC H-2K bm1 gene in murine embryonal carcinoma cells. Nature 310: 415–418, 1984
Sanger, F. and Coulson, A. R.: The use of thin acrylamide gels for DNA sequencing. FEBS Lett. 87: 107–110, 1978
Scott, M. R. D., Westphal, K. H., and Rigby, P. W. J.: Activation of mouse genes in transformed cells. Cell 34: 557–567, 1983
Sege, K., Rask, L., and Peterson, P. A.: Role of β 2-microglobulin in the intracellular processing of HLA antigens. Biochemistry 20: 4550–4556, 1981
Tanaka, K., Appella, E., and Jay, G.: Developmental activation of the H-2K gene is correlated with an increase in DNA methylation. Cell 35: 457–465, 1983
Theiler, K. (ed.): The House Mouse, Springer-Verlag, Heidelberg, 1972
Transy, C., Lalanne, J. L., and Kourilsky, P.: Alternative splicing in the 5′ moiety of the H-2Kd gene transcripts. EMBO J. 10: 2383–2386, 1984
Vasseur, M., Condamine, H., and Duprey, P.: RNAs containing β 2 repeated sequences are transcribed in the early stages of mouse embryogenesis. EMBO J. 4: 1749–1753, 1985
Warner, C. M. and Spannaus, D. J.: Demonstration of H-2 antigens on preimplantation mouse embryos using conventional antisera and monoclonal antibody. J. Exp. Zool. 230: 37–52, 1984
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Morello, D., Duprey, P., Israel, A. et al. Asynchronous regulation of mouse H-2D and beta-2 microglobulin RNA transcripts. Immunogenetics 22, 441–452 (1985). https://doi.org/10.1007/BF00418090
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DOI: https://doi.org/10.1007/BF00418090