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. 1988 Aug 1;168(2):713–724. doi: 10.1084/jem.168.2.713

Immunological responsiveness of neonatal A/J mice to isotypic determinants of syngeneic IgE

PMCID: PMC2188987  PMID: 3411291

Abstract

We have previously shown that adult A/J mice produce high titers of anti-IgE with isotypic or idiotypic specificities in response to challenge with a conjugate of KLH with syngeneic monoclonal IgE. Thus, B cells that can synthesize anti-IgE are present in the mice. Adult mice are unresponsive to unconjugated IgE in CFA, suggesting that tolerance exists at the level of T cells. The present study shows that neonatal mice produce anti-IgE antibodies in response to unconjugated IgE in CFA, but that this capacity is lost after the age of 2-3 wk. The loss of responsiveness corresponds closely with the appearance of detectable IgE in serum, suggesting that the IgE may induce tolerance. The affinities of anti-IgE antibodies produced by neonatal mice fall in the range of values obtained with KLH-IgE in adult mice. Tolerance to unconjugated IgE in CFA can be induced in neonatal mice by administration of IgE in saline. In addition, the tolerant state can be induced by adoptive transfer of spleen cells from adult mice. The time- dependent acquisition of tolerance provides a useful model for studying mechanisms of tolerance and autoimmunity.

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Selected References

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  1. BILLINGHAM R. E., BRENT L., MEDAWAR P. B. Actively acquired tolerance of foreign cells. Nature. 1953 Oct 3;172(4379):603–606. doi: 10.1038/172603a0. [DOI] [PubMed] [Google Scholar]
  2. Bretscher P., Cohn M. A theory of self-nonself discrimination. Science. 1970 Sep 11;169(3950):1042–1049. doi: 10.1126/science.169.3950.1042. [DOI] [PubMed] [Google Scholar]
  3. Cairns L., Rosen F. S., Borel Y. Mice naturally tolerant to C5 have T cells that suppress the response to this antigen. Eur J Immunol. 1986 Oct;16(10):1277–1282. doi: 10.1002/eji.1830161015. [DOI] [PubMed] [Google Scholar]
  4. Champion B. R., Hutchings P., Davies S., Marshall-Clarke S., Cooke A., Roitt I. M. Helper and suppressor activities of an autoreactive mouse thyroglobulin-specific T-cell clone. Immunology. 1986 May;58(1):51–56. [PMC free article] [PubMed] [Google Scholar]
  5. DRESSER D. W. Specific inhibition of antibody production. I. Protein-over loading paralysis. Immunology. 1962 Jan;5:161–168. [PMC free article] [PubMed] [Google Scholar]
  6. Fournié G. J., Lambert P. H., Meischer P. A. Release of DNA in circulating blood and induction of anti-DNA antibodies after injection of bacterial lipopolysaccharides. J Exp Med. 1974 Nov 1;140(5):1189–1206. doi: 10.1084/jem.140.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Green D. R., Flood P. M., Gershon R. K. Immunoregulatory T-cell pathways. Annu Rev Immunol. 1983;1:439–463. doi: 10.1146/annurev.iy.01.040183.002255. [DOI] [PubMed] [Google Scholar]
  8. Haba S., Inada T., Nisonoff A. Quantitative measurements of an intrastrain cross-reactive idiotype in IgE antibodies. J Immunol Methods. 1984 Oct 12;73(1):97–108. doi: 10.1016/0022-1759(84)90035-8. [DOI] [PubMed] [Google Scholar]
  9. Haba S., Nisonoff A. Induction of high titers of anti-IgE by immunization of inbred mice with syngeneic IgE. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5009–5013. doi: 10.1073/pnas.84.14.5009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haba S., Nisonoff A. Production of syngeneic autoreactive monoclonal antibodies specific for isotypic determinants of IgE. J Immunol Methods. 1987 Dec 24;105(2):193–199. doi: 10.1016/0022-1759(87)90266-3. [DOI] [PubMed] [Google Scholar]
  11. Haba S., Nisonoff A. Quantitation of IgE antibodies by radioimmunoassay in the presence of high concentrations of non-IgE antibodies of the same specificity. J Immunol Methods. 1985 Dec 17;85(1):39–52. doi: 10.1016/0022-1759(85)90272-8. [DOI] [PubMed] [Google Scholar]
  12. Haba S., Ovary Z., Nisonoff A. Clearance of IgE from serum of normal and hybridoma-bearing mice. J Immunol. 1985 May;134(5):3291–3297. [PubMed] [Google Scholar]
  13. Haba S., Rosen E. M., Meek K., Nisonoff A. Primary structure of IgE monoclonal antibodies expressing an intrastrain crossreactive idiotype. J Exp Med. 1986 Jul 1;164(1):291–302. doi: 10.1084/jem.164.1.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haba S., Thorbecke G. J., Nisonoff A. Induction and properties of syngeneic murine anti-immunoglobulin D. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2293–2297. doi: 10.1073/pnas.85.7.2293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Harris D. E., Cairns L., Rosen F. S., Borel Y. A natural model of immunologic tolerance. Tolerance to murine C5 is mediated by T cells, and antigen is required to maintain unresponsiveness. J Exp Med. 1982 Aug 1;156(2):567–584. doi: 10.1084/jem.156.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Iverson G. M., Lindenmann J. The role of a carrier-determinant and T cells in the induction of liver-specific autoantibodies in the mouse. Eur J Immunol. 1972 Jun;2(3):195–197. doi: 10.1002/eji.1830020302. [DOI] [PubMed] [Google Scholar]
  17. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  18. Kong Y. M., Okayasu I., Giraldo A. A., Beisel K. W., Sundick R. S., Rose N. R., David C. S., Audibert F., Chedid L. Tolerance to thyroglobulin by activating suppressor mechanisms. Ann N Y Acad Sci. 1982;392:191–209. doi: 10.1111/j.1749-6632.1982.tb36108.x. [DOI] [PubMed] [Google Scholar]
  19. Lukic M. L., Mitchison N. A. Self- and allo-specific suppressor T cells evoked by intravenous injection of F protein. Eur J Immunol. 1984 Aug;14(8):766–768. doi: 10.1002/eji.1830140820. [DOI] [PubMed] [Google Scholar]
  20. Marshall J. S., Bell E. B. Induction of an auto-anti-IgE response in rats I. Effects on serum IgE concentrations. Eur J Immunol. 1985 Mar;15(3):272–277. doi: 10.1002/eji.1830150312. [DOI] [PubMed] [Google Scholar]
  21. Nossal G. J. Cellular mechanisms of immunologic tolerance. Annu Rev Immunol. 1983;1:33–62. doi: 10.1146/annurev.iy.01.040183.000341. [DOI] [PubMed] [Google Scholar]
  22. Owen R. D. IMMUNOGENETIC CONSEQUENCES OF VASCULAR ANASTOMOSES BETWEEN BOVINE TWINS. Science. 1945 Oct 19;102(2651):400–401. doi: 10.1126/science.102.2651.400. [DOI] [PubMed] [Google Scholar]
  23. Robbins P. F., Rosen E. M., Haba S., Nisonoff A. Relationship of VH and VL genes encoding three idiotypic families of anti-p-azobenzenearsonate antibodies. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1050–1054. doi: 10.1073/pnas.83.4.1050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scott D. W., Venkataraman M., Jandinski J. J. Multiple pathways of B lymphocyte tolerance. Immunol Rev. 1979;43:241–280. doi: 10.1111/j.1600-065x.1979.tb00424.x. [DOI] [PubMed] [Google Scholar]
  25. Weigle W. O. Immunological unresponsiveness. Adv Immunol. 1973;16:61–122. doi: 10.1016/s0065-2776(08)60296-5. [DOI] [PubMed] [Google Scholar]

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