Abstract
To study the role of class II MHC expression in mouse lymphomagenesis, we examined the cell surface expression of I-A/E antigens on 24 spontaneous or murine leukemia virus (MuLV)-induced mouse B10.A (I-Ak, I-Ek) B cell lymphomas. Two primary B10.A B cell lymphomas were observed with strong I-Ek expression but with only minimal cell surface I-Ak expression. Both tumors are readily transplantable in syngeneic mice, with maintenance of their I-A-, I-E+ phenotype. Strikingly, one I- A-, I-E+ B cell lymphoma contains a (11; 17) translocation with a breakpoint on chromosome 17 that is localized within or very close to the H-2 complex. DNA of both tumors contains normal restriction enzyme fragments of the A alpha and A beta genes. Northern blot analyses indicated that one I-A-, I-E+ tumor strongly expressed A alpha, E alpha, and E beta mRNAs but possessed only a weak expression of A beta mRNA. The other B cell lymphoma showed A beta, E alpha, and E beta mRNA expression but only minimal A alpha mRNA expression. In 11 primary B10.A B cell lymphomas with a normal I-A+, I-E+ phenotype, no imbalances in A alpha/A beta mRNA levels were observed. The implications of these findings for the role of class II MHC expression in mouse B cell lymphoma-genesis are discussed.
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- Baldacci P., Pozo F., Gisselbrecht S., Kourilsky P. Altered transcription of genes coding for class I histocompatibility antigens in murine tumor cells. J Exp Med. 1983 Oct 1;158(4):1294–1306. doi: 10.1084/jem.158.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bernards R., Schrier P. I., Houweling A., Bos J. L., van der Eb A. J., Zijlstra M., Melief C. J. Tumorigenicity of cells transformed by adenovirus type 12 by evasion of T-cell immunity. 1983 Oct 27-Nov 2Nature. 305(5937):776–779. doi: 10.1038/305776a0. [DOI] [PubMed] [Google Scholar]
- Bono M. R., Strominger J. L. Direct evidence of homology between human DC-1 antigen and murine I-A molecules. Nature. 1982 Oct 28;299(5886):836–840. doi: 10.1038/299836a0. [DOI] [PubMed] [Google Scholar]
- Britt W. J., Chesebro B. H-2D control of recovery from Friend virus leukemia: H-2D region influences the kinetics of the T lymphocyte response to Friend virus. J Exp Med. 1983 Jun 1;157(6):1736–1745. doi: 10.1084/jem.157.6.1736. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chesebro B., Wehrly K. Rfv-1 and Rfv-2, two H-2-associated genes that influence recovery from Friend leukemia virus-induced splenomegaly. J Immunol. 1978 Apr;120(4):1081–1085. [PubMed] [Google Scholar]
- Coffman R. L., Weissman I. L. A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med. 1981 Feb 1;153(2):269–279. doi: 10.1084/jem.153.2.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collins T., Korman A. J., Wake C. T., Boss J. M., Kappes D. J., Fiers W., Ault K. A., Gimbrone M. A., Jr, Strominger J. L., Pober J. S. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4917–4921. doi: 10.1073/pnas.81.15.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Baetselier P., Katzav S., Gorelik E., Feldman M., Segal S. Differential expression of H-2 gene products in tumour cells in associated with their metastatogenic properties. Nature. 1980 Nov 13;288(5787):179–181. doi: 10.1038/288179a0. [DOI] [PubMed] [Google Scholar]
- Debre P., Gisselbrecht S., Pozo F., Levy J. P. Genetic control of sensitivity to Moloney leukemia virus in mice. II. Mapping of three resistant genes within the H-2 complex. J Immunol. 1979 Oct;123(4):1806–1812. [PubMed] [Google Scholar]
- Debré P., Boyer B., Gisselbrecht S., Bismuth A., Lévy J. P. Genetic control of sensitivity to Moloney leukemia virus in mice. III. The three H-2 linked Rmv genes are immune response genes controlling the antiviral antibody response. Eur J Immunol. 1980 Dec;10(12):914–918. doi: 10.1002/eji.1830101205. [DOI] [PubMed] [Google Scholar]
- Festenstein H., Schmidt W. Variation in MHC antigenic profiles of tumor cells and its biological effects. Immunol Rev. 1981;60:85–127. doi: 10.1111/j.1600-065x.1981.tb00363.x. [DOI] [PubMed] [Google Scholar]
- Germain R. N., Ashwell J. D., Lechler R. I., Margulies D. H., Nickerson K. M., Suzuki G., Tou J. Y. "Exon-shuffling" maps control of antibody- and T-cell-recognition sites to the NH2-terminal domain of the class II major histocompatibility polypeptide A beta. Proc Natl Acad Sci U S A. 1985 May;82(9):2940–2944. doi: 10.1073/pnas.82.9.2940. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillies S. D., Folsom V., Tonegawa S. Cell type-specific enhancer element associated with a mouse MHC gene, E beta. Nature. 1984 Aug 16;310(5978):594–597. doi: 10.1038/310594a0. [DOI] [PubMed] [Google Scholar]
- Gooding L. R. Characterization of a progressive tumor from C3H fibroblasts transformed in vitro with SV40 virus. Immunoresistance in vivo correlates with phenotypic loss of H-2Kk. J Immunol. 1982 Sep;129(3):1306–1312. [PubMed] [Google Scholar]
- Herbst E. W., Gropp A., Tietgen C. Chromosome rearrangements involved in the origin of trisomy 15 in spontaneous leukemia of AKR mice. Int J Cancer. 1981 Dec;28(6):805–810. doi: 10.1002/ijc.2910280620. [DOI] [PubMed] [Google Scholar]
- Katzav S., Segal S., Feldman M. Immuno-selection in vivo of H-2D phenotypic variants from a metastatic clone of sarcoma cells results in cell lines of altered metastatic competence. Int J Cancer. 1984 Mar 15;33(3):407–415. doi: 10.1002/ijc.2910330320. [DOI] [PubMed] [Google Scholar]
- Klein G. Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell. 1983 Feb;32(2):311–315. doi: 10.1016/0092-8674(83)90449-x. [DOI] [PubMed] [Google Scholar]
- Klein J., Figueroa F., Klein D. H-2 haplotypes, genes, and antigens: second listing. I. Non-H-2 loci on chromosome 17. Immunogenetics. 1982;16(4):285–317. doi: 10.1007/BF00372302. [DOI] [PubMed] [Google Scholar]
- Koeffler H. P., Ranyard J., Yelton L., Billing R., Bohman R. Gamma-interferon induces expression of the HLA-D antigens on normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4080–4084. doi: 10.1073/pnas.81.13.4080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krajewski A. S., Guy K., Dewar A. E., Cossar D. Immunohistochemical analysis of human MHC class II antigens in B-cell non-Hodgkin's lymphomas. J Pathol. 1985 Feb;145(2):185–194. doi: 10.1002/path.1711450206. [DOI] [PubMed] [Google Scholar]
- Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
- Lemke H., Hämmerling G. J., Hämmerling U. Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice. Immunol Rev. 1979;47:175–206. doi: 10.1111/j.1600-065x.1979.tb00293.x. [DOI] [PubMed] [Google Scholar]
- Lonai P., Katz E., Haran-Ghera N. Role of the major histocompatibility complex in resistance to viral leukemia; its effect on the preleukemic stage of leukemogenesis. Springer Semin Immunopathol. 1982;4(4):373–396. doi: 10.1007/BF02053740. [DOI] [PubMed] [Google Scholar]
- Melief C. J., Vlug A., de Goede R. E., de Bruyne C., Barendsen W., de Greeve P. Naturally occurring leukemia viruses in H-2 congenic C57BL mice. I. High lymphoma incidence following milk-borne transmission of virus. J Natl Cancer Inst. 1980 May;64(5):1179–1189. [PubMed] [Google Scholar]
- Meruelo D. A role for elevated H-2 antigen expression in resistance to neoplasia caused by radiation-induced leukemia virus. Enhancement of effective tumor surveillance by killer lymphocytes. J Exp Med. 1979 Apr 1;149(4):898–909. doi: 10.1084/jem.149.4.898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meruelo D., Leiberman M., Ginzton N., Deak B., McDevitt H. O. Genetic control of radiation leukemia virus-induced tumorigenesis. I. Role of the major murine histocompatibility complex, H-2. J Exp Med. 1977 Oct 1;146(4):1079–1087. doi: 10.1084/jem.146.4.1079. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meruelo D., Nimelstein S. H., Jones P. P., Lieberman M., McDevitt H. O. Increased synthesis and expression of H-2 antigens on thymocytes as a result of radiation leukemia virus infection: a possible mechanism for H-2 linked control of virus-induced neoplasia. J Exp Med. 1978 Feb 1;147(2):470–487. doi: 10.1084/jem.147.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller R., Slamon D. J., Tremblay J. M., Cline M. J., Verma I. M. Differential expression of cellular oncogenes during pre- and postnatal development of the mouse. Nature. 1982 Oct 14;299(5884):640–644. doi: 10.1038/299640a0. [DOI] [PubMed] [Google Scholar]
- Natali P. G., Segatto O., Ferrone S., Tosi R., Corte G. Differential tissue distribution and ontogeny of DC-1 and HLA-DR antigens. Immunogenetics. 1984;19(2):109–116. doi: 10.1007/BF00387853. [DOI] [PubMed] [Google Scholar]
- Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
- Ohno S., Migita S., Wiener F., Babonits M., Klein G., Mushinski J. F., Potter M. Chromosomal translocations activating myc sequences and transduction of v-abl are critical events in the rapid induction of plasmacytomas by pristane and abelson virus. J Exp Med. 1984 Jun 1;159(6):1762–1777. doi: 10.1084/jem.159.6.1762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
- Ozato K., Mayer N. M., Sachs D. H. Monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation. 1982 Sep;34(3):113–120. doi: 10.1097/00007890-198209000-00001. [DOI] [PubMed] [Google Scholar]
- Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
- Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
- Pattengale P. K., Taylor C. R. Experimental models of lymphoproliferative disease. The mouse as a model for human non-Hodgkin's lymphomas and related leukemias. Am J Pathol. 1983 Nov;113(2):237–265. [PMC free article] [PubMed] [Google Scholar]
- Quint W., Boelens W., van Wezenbeek P., Cuypers T., Maandag E. R., Selten G., Berns A. Generation of AKR mink cell focus-forming viruses: a conserved single-copy xenotrope-like provirus provides recombinant long terminal repeat sequences. J Virol. 1984 May;50(2):432–438. doi: 10.1128/jvi.50.2.432-438.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Quint W., Quax W., van der Putten H., Berns A. Characterization of AKR murine leukemia virus sequences in AKR mouse substrains and structure of integrated recombinant genomes in tumor tissues. J Virol. 1981 Jul;39(1):1–10. doi: 10.1128/jvi.39.1.1-10.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robinson R. R., Germain R. N., McKean D. J., Mescher M., Seidman J. G. Extensive polymorphism surrounding the murine Ia A beta chain gene. J Immunol. 1983 Oct;131(4):2025–2031. [PubMed] [Google Scholar]
- Rosloniec E. F., Kuhn M. H., Genyea C. A., Reed A. H., Jennings J. J., Giraldo A. A., Beisel K. W., Lerman S. P. Aggressiveness of SJL/J lymphomas correlates with absence of H-2Ds antigens. J Immunol. 1984 Feb;132(2):945–952. [PubMed] [Google Scholar]
- Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
- Trowbridge I. S., Omary M. B. Molecular complexity of leukocyte surface glycoproteins related to the macrophage differentiation antigen Mac-1. J Exp Med. 1981 Nov 1;154(5):1517–1524. doi: 10.1084/jem.154.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vlug A., Melief C. J., de Bruyne C., Schoenmakers H., Molenaar J. L. Naturally occurring leukemia viruses in H-2 congenic C57BL mice. II. Antibody response to viral envelope antigens. J Natl Cancer Inst. 1980 May;64(5):1191–1198. [PubMed] [Google Scholar]
- Vlug A., Schoenmakers H. J., Melief C. J. Genes of the H-2 complex regulate the antibody response to murine leukemia virus. J Immunol. 1981 Jun;126(6):2355–2360. [PubMed] [Google Scholar]
- Vlug A., Zijlstra M., de Goede R. E., Hesselink W. G., Schoenmakers H. J., Melief C. J. H-2 control of the cytotoxic antibody response against a newly defined MuLV-related cell-surface antigen: G(B10.A). Int J Cancer. 1983 May 15;31(5):617–626. doi: 10.1002/ijc.2910310514. [DOI] [PubMed] [Google Scholar]
- Wallich R., Bulbuc N., Hämmerling G. J., Katzav S., Segal S., Feldman M. Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature. 1985 May 23;315(6017):301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]
- Zijlstra M., de Goede R. E., Schoenmakers H. J., Schinkel A. H., Hesselink W. G., Portis J. L., Melief C. J. Naturally occurring leukemia viruses in H-2 congenic C57BL mice. III. Characterization of C-type viruses isolated from lymphomas induced by milk transmission of B-ecotropic virus. Virology. 1983 Feb;125(1):47–63. doi: 10.1016/0042-6822(83)90062-4. [DOI] [PubMed] [Google Scholar]
- Zijlstra M., de Goede R. E., Schoenmakers H., Radaszkiewicz T., Melief C. J. Ecotropic and dualtropic mink cell focus-inducing murine leukemia viruses can induce a wide spectrum of H-2 controlled lymphoma types. Virology. 1984 Oct 30;138(2):198–211. doi: 10.1016/0042-6822(84)90345-3. [DOI] [PubMed] [Google Scholar]
- van der Hoorn F. A., Lahaye T., Müller V., Ogle M. A., Engers H. D. Characterization of gP85gag as an antigen recognized by Moloney leukemia virus-specific cytolytic T cell clones that function in vivo. J Exp Med. 1985 Jul 1;162(1):128–144. doi: 10.1084/jem.162.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
