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. 1984 Oct;58(1):97–106.

Cell types required for anti-acetylcholine receptor antibody synthesis by cultured thymocytes and blood lymphocytes in myasthenia gravis.

H N Willcox, J Newsom-Davis, L R Calder
PMCID: PMC1576978  PMID: 6236921

Abstract

In most young myasthenia gravis patients, the thymic medulla contains germinal centres. Thymocytes from these cases spontaneously synthesize anti-acetylcholine receptor autoantibody (anti-AChR) in culture; after irradiation they may also selectively stimulate anti-AChR antibody production by autologous blood lymphocytes. By depleting cortical or mature thymic T cells by complement killing, we now show that neither of these responses depends on thymic T cells, unlike the total IgG response to pokeweed mitogen which is T cell-dependent and shows T/B cell synergy. The results suggest that much of the spontaneous anti-AChR production is by autonomous thymic plasma cells, which may be HLA-DR-. The ability to stimulate autologous blood lymphocytes does not require viable HLA-DR+ thymic cells but appears to depend on rare antigen presenting cells from the germinal centres. In preliminary experiments, blood T cells were apparently also necessary.

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Selected References

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

  1. Bastin J. M., Granger S., Tidman N., Janossy G., McMichael A. J. Recognition of a human T-lymphocyte differentiation antigen by an IgM monoclonal antibody. Clin Exp Immunol. 1981 Dec;46(3):597–606. [PMC free article] [PubMed] [Google Scholar]
  2. Bird A. G., Britton S. A new approach to the study of human B lymphocyte function using an indirect plaque assay and a direct B cell activator. Immunol Rev. 1979;45:41–67. doi: 10.1111/j.1600-065x.1979.tb00272.x. [DOI] [PubMed] [Google Scholar]
  3. Bodger M. P., Izaguirre C. A., Blacklock H. A., Hoffbrand A. V. Surface antigenic determinants on human pluripotent and unipotent hematopoietic progenitor cells. Blood. 1983 May;61(5):1006–1010. [PubMed] [Google Scholar]
  4. Charron D. J., McDevitt H. O. Analysis of HLA-D region-associated molecules with monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6567–6571. doi: 10.1073/pnas.76.12.6567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Engel A. G. Morphologic and immunopathologic findings in myasthenia gravis and in congenital myasthenic syndromes. J Neurol Neurosurg Psychiatry. 1980 Jul;43(7):577–589. doi: 10.1136/jnnp.43.7.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gerdes J., Stein H., Mason D. Y., Ziegler A. Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells. Virchows Arch B Cell Pathol Incl Mol Pathol. 1983;42(2):161–172. doi: 10.1007/BF02890379. [DOI] [PubMed] [Google Scholar]
  7. Humphrey J. H., Grennan D. Isolation and properties of spleen follicular dendritic cells. Adv Exp Med Biol. 1982;149:823–827. doi: 10.1007/978-1-4684-9066-4_113. [DOI] [PubMed] [Google Scholar]
  8. Kao I., Drachman D. B. Myasthenic immunoglobulin accelerates acetylcholine receptor degradation. Science. 1977 Apr 29;196(4289):527–529. doi: 10.1126/science.850793. [DOI] [PubMed] [Google Scholar]
  9. Klaus G. G., Humphrey J. H. The generation of memory cells. I. The role of C3 in the generation of B memory cells. Immunology. 1977 Jul;33(1):31–40. [PMC free article] [PubMed] [Google Scholar]
  10. McMichael A. J., Pilch J. R., Galfré G., Mason D. Y., Fabre J. W., Milstein C. A human thymocyte antigen defined by a hybrid myeloma monoclonal antibody. Eur J Immunol. 1979 Mar;9(3):205–210. doi: 10.1002/eji.1830090307. [DOI] [PubMed] [Google Scholar]
  11. Newsom-Davis J., Willcox N., Calder L. Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes. N Engl J Med. 1981 Nov 26;305(22):1313–1318. doi: 10.1056/NEJM198111263052203. [DOI] [PubMed] [Google Scholar]
  12. Okudaira H., Ishizaka K. Reaginic antibody formation in the mouse. XI. Participation of long-lived antibody-forming cells in persistent antibody formation. Cell Immunol. 1981 Feb;58(1):188–201. doi: 10.1016/0008-8749(81)90160-x. [DOI] [PubMed] [Google Scholar]
  13. Osserman K. E., Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med. 1971 Nov-Dec;38(6):497–537. [PubMed] [Google Scholar]
  14. Scadding G. K., Vincent A., Newsom-Davis J., Henry K. Acetylcholine receptor antibody synthesis by thymic lymphocytes: correlation with thymic histology. Neurology. 1981 Aug;31(8):935–943. doi: 10.1212/wnl.31.8.935. [DOI] [PubMed] [Google Scholar]
  15. Thomas J. A., Willcox H. N., Newsom-Davis J. Immunohistological studies of the thymus in myasthenia gravis. Correlation with clinical state and thymocyte culture responses. J Neuroimmunol. 1982 Dec;3(4):319–335. doi: 10.1016/0165-5728(82)90035-2. [DOI] [PubMed] [Google Scholar]
  16. Tidman N., Janossy G., Bodger M., Granger S., Kung P. C., Goldstein G. Delineation of human thymocyte differentiation pathways utilizing double-staining techniques with monoclonal antibodies. Clin Exp Immunol. 1981 Sep;45(3):457–467. [PMC free article] [PubMed] [Google Scholar]
  17. Willcox H. N., Newsom-Davis J., Calder L. R. Greatly increased autoantibody production in myasthenia gravis by thymocyte suspensions prepared with proteolytic enzymes. Clin Exp Immunol. 1983 Nov;54(2):378–386. [PMC free article] [PubMed] [Google Scholar]

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