Abstract
Ongoing, high-titer T-cell-dependent immune responses in adult mice, consisting of IgM, IgG, and IgE anti-fluorescein antibodies, can be specifically and substantially reduced (90-99%) when the mice are injected with appropriate doses of fluoresceinated dextran of defined molecular weight and hapten valence. This suppressive form of the antigen is nontoxic and specific, as responses to other antigens are unaffected. The suppression is long lasting and reduces high-affinity antibodies most markedly. Moreover, plasma cell secretion of specific antibody is virtually eliminated. This demonstrates that the reduction in antibody titer is not simply due to masking of serum antibody by the suppressive polymer. The results are discussed with reference to proposed models of B-cell and T-cell tolerance. Extension of these findings to disease-related immunogens may yield effective antigen-specific treatments of human allergy and autoimmune diseases.
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Selected References
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- Abbas A. K., Klaus G. G., McElroy P. J. Mechanisms of B cell tolerance: I. Dynamic nature of the induction of hapten-specific unresponsiveness by hapten-conjugated pneumococcal polysaccharide. Eur J Immunol. 1977 Jun;7(6):382–387. doi: 10.1002/eji.1830070611. [DOI] [PubMed] [Google Scholar]
- Basten A., Brink R., Peake P., Adams E., Crosbie J., Hartley S., Goodnow C. C. Self tolerance in the B-cell repertoire. Immunol Rev. 1991 Aug;122:5–19. doi: 10.1111/j.1600-065x.1991.tb00593.x. [DOI] [PubMed] [Google Scholar]
- Blaiss M. S., deShazo R. D. Drug allergy. Pediatr Clin North Am. 1988 Oct;35(5):1131–1147. doi: 10.1016/s0031-3955(16)36553-1. [DOI] [PubMed] [Google Scholar]
- Davie J. M., Paul W. E., Katz D. H., Benacerraf B. Hapten-specific tolerance. Preferential depression of the high affinity antibody response. J Exp Med. 1972 Sep 1;136(3):426–438. doi: 10.1084/jem.136.3.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeFranco A. L. Molecular aspects of B-lymphocyte activation. Annu Rev Cell Biol. 1987;3:143–178. doi: 10.1146/annurev.cb.03.110187.001043. [DOI] [PubMed] [Google Scholar]
- Dintzis H. M., Dintzis R. Z. Antigens as immunoregulators. Immunol Rev. 1990 Jun;115:243–251. doi: 10.1111/j.1600-065x.1990.tb00796.x. [DOI] [PubMed] [Google Scholar]
- Dintzis R. Z., Middleton M. H., Dintzis H. M. Studies on the immunogenicity and tolerogenicity of T-independent antigens. J Immunol. 1983 Nov;131(5):2196–2203. [PubMed] [Google Scholar]
- Dintzis R. Z., Okajima M., Middleton M. H., Dintzis H. M. Inhibition of antibody formation by receptor cross-linking: the molecular characteristics of inhibitory haptenated polymers. Eur J Immunol. 1990 Jan;20(1):229–232. doi: 10.1002/eji.1830200133. [DOI] [PubMed] [Google Scholar]
- Dintzis R. Z., Okajima M., Middleton M. H., Greene G., Dintzis H. M. The immunogenicity of soluble haptenated polymers is determined by molecular mass and hapten valence. J Immunol. 1989 Aug 15;143(4):1239–1244. [PubMed] [Google Scholar]
- FELTON L. D., KAUFFMANN G., PRESCOTT B., OTTINGER B. Studies on the mechanism of the immunological paralysis induced in mice by pneumococcal polysaccharides. J Immunol. 1955 Jan;74(1):17–26. [PubMed] [Google Scholar]
- Gherardi E., Pannell R., Milstein C. A single-step procedure for cloning and selection of antibody-secreting hybridomas. J Immunol Methods. 1990 Jan 24;126(1):61–68. doi: 10.1016/0022-1759(90)90012-k. [DOI] [PubMed] [Google Scholar]
- Gleich G. J., Zimmermann E. M., Henderson L. L., Yunginger J. W. Effect of immunotherapy on immunoglobulin E and immunoglobulin G antibodies to ragweed antigens: a six-year prospective study. J Allergy Clin Immunol. 1982 Oct;70(4):261–271. doi: 10.1016/0091-6749(82)90062-8. [DOI] [PubMed] [Google Scholar]
- Golan D. T., Borel Y. Nonantigenicity and immunologic tolerance: the role of the carrier in the induction of tolerance to the hapten. J Exp Med. 1971 Oct 1;134(4):1046–1061. doi: 10.1084/jem.134.4.1046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene G., Hodous J., Dintzis R. Z., Dintzis H. M. Modification, optimization and simplification of the spot ELISA technique for the enumeration of cells secreting anti-hapten antibodies. J Immunol Methods. 1990 May 25;129(2):187–197. doi: 10.1016/0022-1759(90)90438-2. [DOI] [PubMed] [Google Scholar]
- HUMPHREY J. H. IMMUNOLOGICAL UNRESPONSIVENESS TO PROTEIN ANTIGENS IN RABBITS. I. THE DURATION OF UNRESPONSIVENESS FOLLOWING A SINGLE INJECTION AT BIRTH. Immunology. 1964 Jul;7:449–461. [PMC free article] [PubMed] [Google Scholar]
- HayGlass K. T., Stefura W. Isotype-selective abrogation of established IgE responses. Clin Exp Immunol. 1990 Dec;82(3):429–434. doi: 10.1111/j.1365-2249.1990.tb05466.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hornick C. L., Karuch F. Antibody affinity. 3. The role of multivalance. Immunochemistry. 1972 Mar;9(3):325–340. doi: 10.1016/0019-2791(72)90096-1. [DOI] [PubMed] [Google Scholar]
- Howard J. G., Christie G. H., Courtenay B. M. Studies on immunological paralysis. IV. The relative contributions of continuous antibody neutralization and central inhibition to paralysis with type 3 pneumococcal polysaccharide. Proc R Soc Lond B Biol Sci. 1971 Sep 28;178(1053):417–438. doi: 10.1098/rspb.1971.0073. [DOI] [PubMed] [Google Scholar]
- Kemeny D. M., Diaz-Sanchez D. Can persistent IgE responses be suppressed? Clin Exp Immunol. 1990 Dec;82(3):423–426. doi: 10.1111/j.1365-2249.1990.tb05464.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klaus G. G., Abbas A. K., McElroy P. J. Mechanisms of B cell tolerance. II. Evidence for inhibition of antigen receptor expression as a mechanism of unresponsiveness. Eur J Immunol. 1977 Jun;7(6):387–393. doi: 10.1002/eji.1830070612. [DOI] [PubMed] [Google Scholar]
- Klaus G. G., Bijsterbosch M. K., O'Garra A., Harnett M. M., Rigley K. P. Receptor signalling and crosstalk in B lymphocytes. Immunol Rev. 1987 Oct;99:19–38. doi: 10.1111/j.1600-065x.1987.tb01170.x. [DOI] [PubMed] [Google Scholar]
- Kranz D. M., Ballard D. W., Voss E. W., Jr Expression of defined idiotypes throughout the BALB/c anti-fluorescyl antibody response: affinity and idiotype analyses of heterogeneous antibodies. Mol Immunol. 1983 Dec;20(12):1313–1322. doi: 10.1016/0161-5890(83)90162-1. [DOI] [PubMed] [Google Scholar]
- Lee W. Y., Sehon A. H. Suppression of reaging antibody formation. IV. Suppression of reaginic antibodies to penicillin in the mouse. J Immunol. 1976 Sep;117(3):927–934. [PMC free article] [PubMed] [Google Scholar]
- Liu F. T., Bargatze R. F., Katz D. H. Induction of immunologic tolerance to the trimellitate haptenic group in mice: model for a therapeutic approach to trimellitic anhydride-induced hypersensitivity syndromes in humans? J Allergy Clin Immunol. 1980 Oct;66(4):322–326. doi: 10.1016/0091-6749(80)90028-7. [DOI] [PubMed] [Google Scholar]
- MILLER J. J., 3rd AN AUTORADIOGRAPHIC STUDY OF PLASMA CELL AND LYMPHOCYTE SURVIVAL IN RAT POPLITEAL LYMPH NODES. J Immunol. 1964 May;92:673–681. [PubMed] [Google Scholar]
- Naclerio R. M. Allergic rhinitis. N Engl J Med. 1991 Sep 19;325(12):860–869. doi: 10.1056/NEJM199109193251206. [DOI] [PubMed] [Google Scholar]
- 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]
- Nossal G. J. Immunologic tolerance: collaboration between antigen and lymphokines. Science. 1989 Jul 14;245(4914):147–153. doi: 10.1126/science.2526369. [DOI] [PubMed] [Google Scholar]
- Schrader J. W., Nossal G. J. Effector cell blockade. A new mechanism of immune hyporeactivity induced by multivalent antigens. J Exp Med. 1974 Jun 1;139(6):1582–1598. doi: 10.1084/jem.139.6.1582. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H. Acquisition of immunologic self-tolerance. Cell. 1989 Jun 30;57(7):1073–1081. doi: 10.1016/0092-8674(89)90044-5. [DOI] [PubMed] [Google Scholar]
- Siliciano R. F., Colello R. M., Keegan A. D., Dintzis R. Z., Dintzis H. M., Shin H. S. Antigen valence determines the binding of nominal antigen to cytolytic T cell clones. J Exp Med. 1985 Aug 1;162(2):768–773. doi: 10.1084/jem.162.2.768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siliciano R. F., Hemesath T. J., Pratt J. C., Dintzis R. Z., Dintzis H. M., Acuto O., Shin H. S., Reinherz E. L. Direct evidence for the existence of nominal antigen binding sites on T cell surface Ti alpha-beta heterodimers of MHC-restricted T cell clones. Cell. 1986 Oct 24;47(2):161–171. doi: 10.1016/0092-8674(86)90439-3. [DOI] [PubMed] [Google Scholar]
- Siliciano R. F., Keegan A. D., Dintzis R. Z., Dintzis H. M., Shin H. S. The interaction of nominal antigen with T cell antigen receptors. I. Specific binding of multivalent nominal antigen to cytolytic T cell clones. J Immunol. 1985 Aug;135(2):906–914. [PubMed] [Google Scholar]
- Vieira P., Rajewsky K. The half-lives of serum immunoglobulins in adult mice. Eur J Immunol. 1988 Feb;18(2):313–316. doi: 10.1002/eji.1830180221. [DOI] [PubMed] [Google Scholar]