Abstract
Immunization of mice with a combination of passively administered syngeneic IgG (anti-p-azophenylarsonate [anti-Ars]) antibody and a soluble, multivalent form of the antibody's corresponding antigen (Limulus polyphemus hemocyanin conjugated with Ars [Lph-Ars]) resulted in specific autoanti-IgG Fc (rheumatoid factor) production. The response was rapid and only anti-IgG of the IgM isotype is found. Because immunization with either the IgG antibody or the antigen alone did not result in rheumatoid antibody production, immune complexes appear to be the active form of the immunogens. Antibody/antigen ratios that resulted in maximal anti-IgG antibody responses were the same as those required for peak in vitro immunoprecipitation, i.e., equivalence. Previous exposure of the mice to the exogenously supplied antigen was not required for the response. The response to immune complexes is specific because mice immunized with IgG2a-containing complexes produced autoanti-IgG2a, while mice immunized with IgG1- containing complexes produced anti-IgG1 with little reactivity to other IgG isotypes. IgG2a blocked in its complement-fixing capacity was more effective in eliciting the anti-IgG2a response than native IgG2a, suggesting a possible role for the complement system in modulating the anti-IgG2a response. Induction of rheumatoid factor production by immune complexes could be induced in xid mice but not in nu/nu mice, indicating T lymphocyte dependence of the response. In contrast, the B lymphocyte activator lipopolysaccharide was able to elicit vigorous rheumatoid factor production in both nu/nu and normal mice, demonstrating that nu/nu mice contain B cells capable of making the response. Rheumatoid antibody produced in the immune complex- or LPS- induced responses is Fc specific and has relatively low affinity for IgG that is not bound to antigen.
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Selected References
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- Bach B. A., Sherman L., Benacerraf B., Greene M. I. Mechanisms of regulation of cell-mediated immunity. II. Induction and suppression of delayed-type hypersensitivity to azobenzenearsonate-coupled syngeneic cells. J Immunol. 1978 Oct;121(4):1460–1468. [PubMed] [Google Scholar]
- Coulie P., Van Snick J. Rheumatoid factors and secondary immune responses in the mouse. II. Incidence, kinetics and induction mechanisms. Eur J Immunol. 1983 Nov;13(11):895–899. doi: 10.1002/eji.1830131107. [DOI] [PubMed] [Google Scholar]
- Cunningham A. J., Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed] [Google Scholar]
- Dresser D. W. Most IgM-producing cells in the mouse secrete auto-antibodies (rheumatoid factor). Nature. 1978 Aug 3;274(5670):480–483. doi: 10.1038/274480a0. [DOI] [PubMed] [Google Scholar]
- Hang L., Theofilopoulos A. N., Dixon F. J. A spontaneous rheumatoid arthritis-like disease in MRL/l mice. J Exp Med. 1982 Jun 1;155(6):1690–1701. doi: 10.1084/jem.155.6.1690. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Izui S., Eisenberg R. A., Dixon F. J. IgM rheumatoid factors in mice injected with bacterial lipopolysaccharides. J Immunol. 1979 May;122(5):2096–2102. [PubMed] [Google Scholar]
- Keightley R. G., Cooper M. D., Lawton A. R. The T cell dependence of B cell differentiation induced by pokeweed mitogen. J Immunol. 1976 Nov;117(5 Pt 1):1538–1544. [PubMed] [Google Scholar]
- Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshak-Rothstein A., Siekevitz M., Margolies M. N., Mudgett-Hunter M., Gefter M. L. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120–1124. doi: 10.1073/pnas.77.2.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morgan E. L., Weigle W. O. Aggregated human gamma-globulin-induced proliferation and polyclonal activation of murine B lymphocytes. J Immunol. 1980 Jul;125(1):226–231. [PubMed] [Google Scholar]
- Morgan E. L., Weigle W. O. Polyclonal activation of murine B lymphocytes by immune complexes. J Immunol. 1983 Mar;130(3):1066–1070. [PubMed] [Google Scholar]
- Nemazee D. A., Sato V. L. Enhancing antibody: a novel component of the immune response. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3828–3832. doi: 10.1073/pnas.79.12.3828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nemazee D. A., Sato V. L. Induction of rheumatoid antibodies in the mouse. Regulated production of autoantibody in the secondary humoral response. J Exp Med. 1983 Aug 1;158(2):529–545. doi: 10.1084/jem.158.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Popham A. M., Dresser D. W. Rheumatoid factors in mice: non-specific activators of heterophile rheumatoid factor production. Immunology. 1980 Nov;41(3):579–585. [PMC free article] [PubMed] [Google Scholar]
- SCHUR P. H., CHRISTIAN G. D. THE ROLE OF DISULFIDE BONDS IN THE COMPLEMENT-FIXING AND PRECIPITATING PROPERTIES OF 7S RABBIT AND SHEEP ANTIBODIES. J Exp Med. 1964 Oct 1;120:531–545. doi: 10.1084/jem.120.4.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scher I. The CBA/N mouse strain: an experimental model illustrating the influence of the X-chromosome on immunity. Adv Immunol. 1982;33:1–71. doi: 10.1016/s0065-2776(08)60834-2. [DOI] [PubMed] [Google Scholar]
- Sweet G. H., Welborn F. L. Use of chromium chloride as the coupling agent in a modified plaque assay. Cells producing anti-protein antibody. J Immunol. 1971 May;106(5):1407–1410. [PubMed] [Google Scholar]
- Van Snick J. L., Coulie P. Monoclonal anti-IgG autoantibodies derived from lipopolysaccharide-activated spleen cells of 129/Sv mice. J Exp Med. 1982 Jan 1;155(1):219–230. doi: 10.1084/jem.155.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wysocki L. J., Sato V. L. The strain A anti-p-azophenylarsonate major cross-reactive idiotypic family includes members with no reactivity toward p-azophenylarsonate. Eur J Immunol. 1981 Oct;11(10):832–839. doi: 10.1002/eji.1830111016. [DOI] [PubMed] [Google Scholar]
- van Snick J. L., Masson P. L. Age-dependent production of IgA and IgM autoantibodies against IgG2a in a colony of 129/Sv mice. J Exp Med. 1979 Jun 1;149(6):1519–1530. doi: 10.1084/jem.149.6.1519. [DOI] [PMC free article] [PubMed] [Google Scholar]