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. 1974 Mar 1;139(3):643–660. doi: 10.1084/jem.139.3.643

ROLES OF T AND B LYMPHOCYTES IN THE TERMINATION OF UNRESPONSIVENESS TO AUTOLOGOUS THYROGLOBULIN IN MICE

James A Clagett 1, William O Weigle 1
PMCID: PMC2139539  PMID: 4591173

Abstract

The data presented in this paper support the hypothesis that unresponsiveness to autologous thyroglobulin (Tg) exists in the T cells and responsiveness exists in the B cells. Such a conclusion is based on the results of antigen-binding studies where few, if any, thymocytes recognized syngeneic Tg. Comparable numbers of antigen-binding lymphocytes for syngeneic Tg were found in the spleens of normal intact mice and of nude mice. The latter fact suggested that B cells exist which recognize self-constituents. From antigen-suicide experiments, a clearer picture of the susceptibility of B cells to iodinated self-antigen and of the obligatory role of antibody in the induction of lesions was developed. Only bone marrow cells (B cells) were affected by [125I]syngeneic Tg, in which case the incidence of lesions was diminished. From adoptive transfer experiments, the results demonstrate that unresponsiveness may be terminated by immunization with a mixture of heterologous (cross-reacting) Tg's. In this situation T cells are required since a B-cell reconstituted host failed to make antibody (plaque-forming cells) and to develop lesions. T cells in this form of an unresponsive state may recognize determinants on the heterologous Tg unrelated to autologous Tg and as such stimulate the normal complement of B cells to produce antibody that both reacts with autologous and heterologous Tg.

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Selected References

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  1. Bankhurst A. D., Torrigiani G., Allison A. C. Lymphocytes binding human thyroglobulin in healthy people and its relevance to tolerance for autoantigens. Lancet. 1973 Feb 3;1(7797):226–230. doi: 10.1016/s0140-6736(73)90066-4. [DOI] [PubMed] [Google Scholar]
  2. Basten A., Miller J. F., Warner N. L., Pye J. Specific inactivation of thymus-derived (T) and non-thymus-derived (B) lymphocytes by 125I-labelled antigen. Nat New Biol. 1971 May 26;231(21):104–106. doi: 10.1038/newbio231104a0. [DOI] [PubMed] [Google Scholar]
  3. Byrt P., Ada G. L. An in vitro reaction between labelled flagellin or haemocyanin and lymphocyte-like cells from normal animals. Immunology. 1969 Oct;17(4):503–516. [PMC free article] [PubMed] [Google Scholar]
  4. COCHRANE C. G., UNANUE E. R., DIXON F. J. A ROLE OF POLYMORPHONUCLEAR LEUKOCYTES AND COMPLEMENT IN NEPHROTOXIC NEPHRITIS. J Exp Med. 1965 Jul 1;122:99–116. doi: 10.1084/jem.122.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiller J. M., Habicht G. S., Weigle W. O. Cellular sites of immunologic unresponsiveness. Proc Natl Acad Sci U S A. 1970 Mar;65(3):551–556. doi: 10.1073/pnas.65.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Claman H. N., Chaperon E. A., Triplett R. F. Thymus-marrow cell combinations. Synergism in antibody production. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1167–1171. doi: 10.3181/00379727-122-31353. [DOI] [PubMed] [Google Scholar]
  7. Clinton B. A., Weigle W. E. Cellular events during the induction of experimental thyroiditis in the rabbit. J Exp Med. 1972 Dec 1;136(6):1605–1615. doi: 10.1084/jem.136.6.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davie J. M., Paul W. E. Receptors on immunocompetent cells. II. Specificity and nature of receptors on dinitrophenylated guinea pig albumin- 125 I-binding lymphocytes of normal guinea pigs. J Exp Med. 1971 Aug 1;134(2):495–516. doi: 10.1084/jem.134.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dwyer J. M., Mackay I. R. Validation of autoradiography for recognition of antigen-binding lymphocytes in blood and lymphoid tissues. Quantitation and specificity of binding. Clin Exp Immunol. 1972 Apr;10(4):581–597. [PMC free article] [PubMed] [Google Scholar]
  10. Dwyer J. M., Mason S., Warner N. L., Mackay I. R. Antigen binding lymphocytes in congenitally athymic (nude) mice. Nat New Biol. 1971 Dec 22;234(51):252–253. doi: 10.1038/newbio234252a0. [DOI] [PubMed] [Google Scholar]
  11. FARR R. S. A quantitative immunochemical measure of the primary interaction between I BSA and antibody. J Infect Dis. 1958 Nov-Dec;103(3):239–262. doi: 10.1093/infdis/103.3.239. [DOI] [PubMed] [Google Scholar]
  12. FERRARI A. Nitrogen determination by a continuous digestion and analysis system. Ann N Y Acad Sci. 1960 Jul 22;87:792–800. doi: 10.1111/j.1749-6632.1960.tb23236.x. [DOI] [PubMed] [Google Scholar]
  13. Golub E. S., Mishell R. I., Weigle W. O., Dutton R. W. A modification of the hemolytic plaque assay for use with protein antigens. J Immunol. 1968 Jan;100(1):133–137. [PubMed] [Google Scholar]
  14. Henson P. M. Pathologic mechanisms in neutrophil-mediated injury. Am J Pathol. 1972 Sep;68(3):593–612. [PMC free article] [PubMed] [Google Scholar]
  15. Hämmerling G. J., Masuda T., McDevitt H. O. Genetic control of the immune response. Frequency and characteristics of antigen-binding cells in high and low responder mice. J Exp Med. 1973 May 1;137(5):1180–1200. doi: 10.1084/jem.137.5.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. JERNE N. K., NORDIN A. A. Plaque formation in agar by single antibody-producing cells. Science. 1963 Apr 26;140(3565):405–405. [PubMed] [Google Scholar]
  17. Lawrence D. A., Spiegelberg H. L., Weigle W. O. 2,4-Dinitrophenyl receptors on mouse thymus and spleen cells. J Exp Med. 1973 Feb 1;137(2):470–482. doi: 10.1084/jem.137.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MCMASTER P. R., LERNER E. M., 2nd, EXUM E. D. The relationship of delayed hypersensitivity and circulating antibody to experimental allergic thyroditis in inbred guinea pigs. J Exp Med. 1961 Apr 1;113:611–624. doi: 10.1084/jem.113.4.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
  20. McLaughlin J. F., Paterson P. Y., Hartz R. S., Embury S. H. Rheumatic carditis: in vitro responses of peripheral blood leukocytes to heart and streptococcal antigens. Arthritis Rheum. 1972 Nov-Dec;15(6):600–608. doi: 10.1002/art.1780150606. [DOI] [PubMed] [Google Scholar]
  21. Miller J. F., Mitchell G. F. The thymus and the precursors of antigen reactive cells. Nature. 1967 Nov 18;216(5116):659–663. doi: 10.1038/216659a0. [DOI] [PubMed] [Google Scholar]
  22. Modabber F., Morikawa S., Coons A. H. Antigen-binding cells in normal mouse thymus. Science. 1970 Dec 4;170(3962):1102–1104. doi: 10.1126/science.170.3962.1102. [DOI] [PubMed] [Google Scholar]
  23. Nakamura R. M., Weigle W. O. Experimental thyroiditis in complement intact and deficient mice following injections of heterologous thyroglobulins without adjuvant. Proc Soc Exp Biol Med. 1968 Nov;129(2):412–416. doi: 10.3181/00379727-129-33333. [DOI] [PubMed] [Google Scholar]
  24. Nakamura R. M., Weigle W. O. Transfer of experimental autoimmune thyroiditis by serum from thyroidectomized donors. J Exp Med. 1969 Aug 1;130(2):263–285. doi: 10.1084/jem.130.2.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Romagnani S., Ricci M., Passaleva A., Biliotti G. Cell-mediated immune responses to heterologous and homologous thyroglobulin in guinea-pigs immunized with heterologous thyroid extracts. Immunology. 1970 Oct;19(4):599–612. [PMC free article] [PubMed] [Google Scholar]
  26. Rose N. R., Stylos W. A. Splitting of human thyroglobulin. I. Reduction and alkylation. Clin Exp Immunol. 1969 Jul;5(1):129–140. [PMC free article] [PubMed] [Google Scholar]
  27. Unanue E. R. Antigen binding cells. II. Effect of highly radioactive antigen on the immunologic function of bone marrow cells. J Immunol. 1971 Dec;107(6):1663–1665. [PubMed] [Google Scholar]
  28. Vladutiu A. O., Rose N. R. Transfer of experimental autoimmune thyroiditis of the mouse by serum. J Immunol. 1971 Apr;106(4):1139–1142. [PubMed] [Google Scholar]
  29. WEIGLE W. O. THE INDUCTION OF AUTOIMMUNITY IN RABBITS FOLLOWING INJECTION OF HETEROLOGOUS OR ALTERED HOMOLOGOUS THYROGLOBULIN. J Exp Med. 1965 Feb 1;121:289–308. doi: 10.1084/jem.121.2.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Warner N. L., Byrt P., Ada G. L. Blocking of the lymphocyte antigen receptor site with anti-immunoglobulin sera in vitro. Nature. 1970 Jun 6;226(5249):942–943. doi: 10.1038/226942a0. [DOI] [PubMed] [Google Scholar]
  31. Wick G., Kite J. H., Jr, Cole R. K., Witebsky E. Spontaneous thyroiditis in the obese strain of chickens. 3. The effect of bursectomy on the development of the disease. J Immunol. 1970 Jan;104(1):45–53. [PubMed] [Google Scholar]

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