Abstract
Different immunoglobulin preparations of human monoclonal IgM, normal human and rat IgG, as well as purified rabbit antibodies were treated by various methods, fragmentation, aggregation and complexing with antigen. The ability of the treated and untreated preparations to fix isolated human C1, to activate the classical complement pathway (to consume C4 in normal human serum) were compared. It was found that the different methods affected the conformation of the immunoglobulin molecules in different ways and induced changes to a greater or lesser extent in the two capacities of the preparations tested. In the case of the monoclonal IgM preparation a strong C1-fixation was observed without measurable complement activation. Other preparations, interfacially aggregated human IgG, BSA-anti-BSA and OA-anti-OA immune complexes had a very weak C1-fixing but a marked complement activating capacity. Some preparations, e.g. heat-aggregated IgG, both fixed and activated C1 effectively, aggregates with a complement-activating capacity without C1-fixing effect were separated by gel-filtration. It was demonstrated further, that at a given time only a part of the activated C1 molecules could be found fixed to the immunoglobulins, the other part was released into the fluid phase after activation. On the basis of the results of this and previous studies a hypothesis is proposed suggesting three possible results of the interaction between C1 and the different preparations: (1) firm fixation and activation; (2) binding not followed by activation and (3) a transient binding leading to activation. The possible application of this hypothesis for the interpretation of the results of the different methods for detecting immune complexes is discussed.
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Selected References
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- Allan R., Isliker H. Studies on the complement-binding site of rabbit immunoglobulin G. I. Modification of tryptophan residues and their role in anticomplementary activity of rabbit IgG. Immunochemistry. 1974 Apr;11(4):175–180. doi: 10.1016/0019-2791(74)90325-5. [DOI] [PubMed] [Google Scholar]
- Augener W., Grey H. M., Cooper N. R., Müller-Eberhard H. J. The reaction of monomeric and aggregated immunoglobulins with C1. Immunochemistry. 1971 Nov;8(11):1011–1020. doi: 10.1016/0019-2791(71)90489-7. [DOI] [PubMed] [Google Scholar]
- Borsos T., Rapp H. J. Immune hemolysis: a simplified method for the preparation of EAC'4 with guinea pig or with human complement. J Immunol. 1967 Aug;99(2):263–268. [PubMed] [Google Scholar]
- Casali P., Bossus A., Carpentier N. A., Lambert P. H. Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test. A comparative study with 125I-labelled Clq binding and Raji-cell RIA tests. Clin Exp Immunol. 1977 Aug;29(2):342–354. [PMC free article] [PubMed] [Google Scholar]
- Füst G., Csécsi-Nagy M., Medgyesi G. A., Kulics J., Gergely J. Study of the interaction between monoclonal IgM proteins and the complement system. Immunochemistry. 1976 Oct;13(10):793–800. doi: 10.1016/0019-2791(76)90178-6. [DOI] [PubMed] [Google Scholar]
- Hodgson H. J., Potter B. J., Jewell D. P. Immune complexes in ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1977 Aug;29(2):187–196. [PMC free article] [PubMed] [Google Scholar]
- Hurst M. M., Volanakis J. E., Stroud R. M., Bennett J. C. C1 fixation and classical complement pathway activation by a fragment of the Cmu4 domain of IgM. J Exp Med. 1975 Nov 1;142(5):1322–1326. doi: 10.1084/jem.142.5.1322. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson A. H., Mowbray J. F., Porter K. A. Detection of circulating immune complexes in pathological human sera. Lancet. 1975 Apr 5;1(7910):762–765. doi: 10.1016/s0140-6736(75)92433-2. [DOI] [PubMed] [Google Scholar]
- Miekka S. I., Gozze I. Anticomplementary activity of human immunoglobulin G. I. Mechanism of the artifactual increase in anticomplementary activity of IgG during the assay. Vox Sang. 1975;29(2):101–123. doi: 10.1111/j.1423-0410.1975.tb00485.x. [DOI] [PubMed] [Google Scholar]
- Müller-Eberhard H. J. Complement. Annu Rev Biochem. 1975;44:697–724. doi: 10.1146/annurev.bi.44.070175.003405. [DOI] [PubMed] [Google Scholar]
- Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
- Nydegger U. E., Lambert P. H., Gerber H., Miescher P. A. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q. J Clin Invest. 1974 Aug;54(2):297–309. doi: 10.1172/JCI107765. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Siegel J., Rent R., Gewurz H. Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera. J Exp Med. 1974 Sep 1;140(3):631–647. doi: 10.1084/jem.140.3.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sobel A. T., Bokisch V. A., Müller-Eberhard H. J. C1q deviation test for the detection of immune complexes, aggregates of IgG, and bacterial products in human serum. J Exp Med. 1975 Jul 1;142(1):139–150. doi: 10.1084/jem.142.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soter N. A., Austen K. F., Gigli I. Inhibition by epsilon-aminocaproic acid of the activation of the first component of the complement system. J Immunol. 1975 Mar;114(3):928–932. [PubMed] [Google Scholar]
- Tamura N., Nelson R. A., Jr The purification and reactivity of the first component of complement from guinea pig, human and canine sera. J Immunol. 1968 Dec;101(6):1333–1345. [PubMed] [Google Scholar]
- Theofilopoulos A. N., Wilson C. B., Bokisch V. A., Dixon F. J. Binding of soluble immune complexes to human lymphoblastoid cells. II. Use of Raji cells to detect circulating immune complexes in animal and human sera. J Exp Med. 1974 Nov 1;140(5):1230–1244. doi: 10.1084/jem.140.5.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thompson J. J., Hoffmann L. G. Cooperative binding of a complement component to antigen-antibody complexes--I: complexes containing rabbit IgG antibody. Immunochemistry. 1974 Aug;11(8):431–445. doi: 10.1016/0019-2791(74)90077-9. [DOI] [PubMed] [Google Scholar]
- Zubler R. H., Lange G., Lambert P. H., Miescher P. A. Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus. J Immunol. 1976 Jan;116(1):232–235. [PubMed] [Google Scholar]