Abstract
Nonlymphoid, stromal cells in the mouse thymus are believed to be important in T cell maturation and have been proposed to play a central role in the acquisition of major histocompatibility complex (MHC) restriction and self-tolerance by maturing thymocytes. Both cortical and medullary epithelial cells in the thymus express high levels of class II (A) major histocompatibility antigens (MHC Ags). We show here that a specific subset of these A− epithelial cells express a transformation-associated antigen (6C3Ag) found previously on the surfaces of Abelson murine leukemia virus-transformed pre-B cells and on those bone marrow-derived stromal cell clones which support normal and preneoplastic pre-B cell proliferation. Among solid lymphoid organs, only the thymus contains 6C3Ag1 cells and within the thymus, this antigen is found exclusively on A− epithelial cells in cortical regions. It is striking that the expression of the 6C3Ag on thymic epithelium is developmentally regulated, suggesting a role for this lymphostromal antigen in the maturation of the thymic microenvironment.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adkins, B., Mueller, C., Okada, C. Y., Reichert, R. A., Weissman, I. L., and Spangrude, G. J.: Early events in T cell maturation. Annu. Rev. Immunol. 5: 325–365, 1987
Andrews, P. and Boyd, R. L.: The murine thymic nurse cell: an isolated thymic microenvironment. Eur. J. Immunol. 15: 36–42, 1985
Bach, J. R., Dardenne, M., Pleau, J. M., and Bach, M. A.: Isolation, biochemical characteristics and biological activity of a circulating thymic hormone in the mouse and in the human. Ann. N. Y. Acad. Sci. 249: 186–210, 1975
Barclay, A. N. and Mayrhofer, G.: Bone marrow origin of la-positive cells in the medulla of rat thymus. J. Exp. Med. 153: 1666–1671, 1981
Bryant, B. J.: Renewal and fate in the mammalian thymus. Mechanisms and interferences of thymokinetics. Eur. J. Immunol. 2: 38–45, 1972
Cantor, H. and Weissman, I.: Development and function of subpopulation of thymocytes and T lymphocytes. Prog. Allergy 20: 1–64, 1976
Duijvestijn, A. M., Schutte, R., Kohler, Y. G., Korn, G., and Hoefsmit, E. C. M.: Characterization of the population of phagocytic cells in thymic cell suspension. A morphological and cytochemical study. Cell Tissue Res. 231: 313–323, 1983
Elder, J. H. and Alexander, S.: Endo-β-N-acetylglucosaminidase F: endoglycosidase from Flavobacterium Meningosepticum that cleaves both high-mannose and complex glycoproteins. Proc. Natl. Acad. Sci. U.S.A. 79: 4540–4544, 1982
Fink, P. J. and Bevan, M. J.: H-2 antigens of the thymus determine lymphocyte specificity. J. Exp. Med. 148: 766–775, 1978
Fink, P. J., Weissman, I. L., Kaplan, H. S., and Kyewski, B. A.: The immunocompetence of murine stromal cell-associated thymocytes. J. Immunol. 132: 2266–2272, 1984
Hardy, R.: Purification and coupling of fluorescent proteins for use in flow cytometry. In D. M. Weir, L. A. Herzenberg, C. Blackwell, and L. A. Herzenberg (eds.): Handbook of Experimental Immunolo-gy, fourth edition, pp. 146–155, Blackwell Scientific Publications, Oxford, Boston, 1986
Jenkinson, E. J., van Ewijk, W., and Owen, J. J. T.: Major histocompatibility antigen expression on the epithelium of the developing thymus in normal and nude mice. J. Exp. Med. 153: 280–292, 1981
Kappler, J. W., Skidmore, B., White, J., and Marrack, P.: Antigen-inducible, H-2 restricted, interleukin-2-producing T cell hybridomas. J. Exp. Med. 153: 1198–1214, 1981
Kruisbeek, A. M.: Thymic factors and T cell maturation in vitro: a comparison of the effects of thymic epithelial cultures with thymic extracts and thymus dependent serum factors. Thymus 1: 163–185, 1979
Kyewski, B. A. and Kaplan, H. S.: Lymphoepithelial interactions in the mouse thymus: phenotypic and kinetic studies on thymic nurse cells. J. Immunol. 128: 2287–2294, 1982
Kyewski, B. A., Fathman, C. G., and Rouse, R. V.: Intrathymic presen-tation of circulating non-MHC antigens by medullary dendritic cells. J. Exp. Med. 163: 231–246, 1986
Laemmli, U. K.: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227 680–685, 1970
Lostrum, M. W., Stone, M. R., Tam, M., Burnette, W. N., Pinter, A., and Nowinski, R. C.: Monoclonal antibodies against murine leukemia viruses: identification of the six antigenic determinants on the P15(e) and gp70 envelope protein. Virology 98: 336–350, 1979
Morse, H. C., III, Tidmarsh, G. F., Holmes, K. L., Fredrickson, T. N., Hartley, J. W., Pierce, J. H., Langdon, W. Y., Dailey, M. O., and Weissman, I. L.: Expression of the 6C3 antigen on murine hematopoietic neoplasms: association with expression of abl, ras, fes, src, erbB and Cas NS-1 oncogenes but not with myc. J. Exp. Med. 165: 920, 1987
Muller-Sieburg, C. E., Whitlock, C. A., and Weissman, I. L.: Isolation of two early B lymphocyte progenitors from mouse marrow: a committed PRE-PRE-B cell and a clonogenic Thy-1lo hematopoietic stem cell. Cell 44: 653–662, 1986
Pillemer, E., Whitlock, C., and Weissman, I.: Transformationassociated proteins in murine B-cell lymphomas that are distinct from Abelson gene products. Proc. Natl. Acad. Sci. U.S.A 81: 4434–4438, 1984
Reichert, R. A., Gallatin, W. M., Butchert, E. C., and Weissman, I. L.: A homing receptor-bearing cortical thymocyte subset: implications for thymus cell migration and the nature of cortisone-resistant thymocytes. Cell 38: 89–99, 1984
Rouse, R. V., van Ewijk, W., Jones, P. P., and Weissman, I. L.: Expression of MHC antigens by mouse thymic dendritic cells. J. Immunol. 122: 2508–2515, 1979
Rouse, R. V., Ezine, S., and Weissman, I. L.: Expression of major histocompatibility complex antigens in the thymuses of chimeric mice. Transplantation 40: 422–426, 1985
Sharrow, A. O., Mathieson, B. J., and Singer, A.: Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras. J. Immunol. 126: 1327–1335, 1981
Tidmarsh, G. F., Dailey, M. O., Whitlock, C. A., Pillemer, E., and Weissman, I. L.: Transformed lymphocytes from Abelson-diseased mice express levels of a B lineage transformation-associated antigen elevated from that found on normal lymphocytes. J. Exp. Med. 162: 1421–1434, 1985
Tidmarsh, G. F., Dailey, M. O., and Weissman, I. L.: Expression of a monoclonal antibody defined B-lineage transformation antigen specifically identifies Abelson diseased mice. J. Exp. Med. 164: 1356–1361, 1986
van Ewijk, W., Rouse, R. V., and Weissman, I. L.: Distribution of H-2 microenvironments in the mouse thymus. Immunoelectron microscopic identification of 1-A and H-2K bearing cells. J. Histochem. Cytochem. 28: 1089–1099, 1980
van Vliet, E., Melis, M., and van Ewijk, W.: Immunohistology of thymic nurse cells. Cell. Immunol. 87: 101–109, 1984a
van Vliet, E., Melis, M., and van Ewijk, W.: Monoclonal antibodies to stromal cell types of the mouse thymus. Eur. J. Immunol. 14: 524–529, 1984b
van Vliet, E., Jenkinson, E. J., Kingston, R., Owen, J. J. T., and van Ewijk, W.: Stromal cell types in the developing thymus of the normal and nude mouse embryo. Eur. J. Immunol. 15: 675–681, 1985
Wekerle, H., Kerelsen, U.-P., and Ernst, M.: Thymic nurse cells. Lymphoepithelial cell complexes in murine thymus: morphological and serological characterization. J. Exp. Med. 151: 925–944, 1980
Whitlock, C. A., Tidmarsh, G. F., Muller-Sieburg, C., and Weissman, I. L.: Bone marrow stromal cell lines with lymphopoietic activity express high levels of a pre-B neoplasia-associated molecule. Cell 48: 1009–1021, 1987
Witte, O. N. and Weissman, I. L.: Membrane proteins of MSV-MLV: their role in virion-virion interactions in vitro. Virology 61: 588–593, 1974
Zinkernagel, R. M. and Doherty, P. C.: MHC-restricted T cells: studies on the biological role of polymorphic major transplantation antigens determining T cell restriction-specificity, Adv. Immunol. function, and responsiveness. 27: 51–177, 1980
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Adkins, B., Tidmarsh, G.F. & Weissman, I.L. Normal thymic cortical epithelial cells developmentally regulate the expression of a B-lineage transformation-associated antigen. Immunogenetics 27, 180–186 (1988). https://doi.org/10.1007/BF00346584
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00346584