Abstract
An animal model has been used to address the question of the biological importance of the known structural difference between the two isotypes of human C4, i.e., C4A and C4B. Guinea pigs deficient in C4 were reconstituted transiently with either human C4A or C4B protein and immunized with the bacteriophage phi X174. Results from this study showed that C4A-reconstituted animals made a secondary response, i.e., switch from IgM to IgG; whereas the C4B-reconstituted animals did not.
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- Air G. M. Amino acid sequences from the gene F (capsid) protein of bacteriophage phiX174. J Mol Biol. 1976 Nov 15;107(4):433–443. doi: 10.1016/s0022-2836(76)80076-9. [DOI] [PubMed] [Google Scholar]
- Awdeh Z. L., Alper C. A. Inherited structural polymorphism of the fourth component of human complement. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3576–3580. doi: 10.1073/pnas.77.6.3576. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
- Belt K. T., Carroll M. C., Porter R. R. The structural basis of the multiple forms of human complement component C4. Cell. 1984 Apr;36(4):907–914. doi: 10.1016/0092-8674(84)90040-0. [DOI] [PubMed] [Google Scholar]
- Belt K. T., Yu C. Y., Carroll M. C., Porter R. R. Polymorphism of human complement component C4. Immunogenetics. 1985;21(2):173–180. doi: 10.1007/BF00364869. [DOI] [PubMed] [Google Scholar]
- Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
- Bishof N. A., Welch T. R., Beischel L. S. C4B deficiency: a risk factor for bacteremia with encapsulated organisms. J Infect Dis. 1990 Jul;162(1):248–250. doi: 10.1093/infdis/162.1.248. [DOI] [PubMed] [Google Scholar]
- Braun L., Schneider P. M., Giles C. M., Bertrams J., Rittner C. Null alleles of human complement C4. Evidence for pseudogenes at the C4A locus and for gene conversion at the C4B locus. J Exp Med. 1990 Jan 1;171(1):129–140. doi: 10.1084/jem.171.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buus S., Colon S., Smith C., Freed J. H., Miles C., Grey H. M. Interaction between a "processed" ovalbumin peptide and Ia molecules. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3968–3971. doi: 10.1073/pnas.83.11.3968. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carroll M. C., Belt K. T., Palsdottir A., Yu Y. Molecular genetics of the fourth component of human complement and steroid 21-hydroxylase. Immunol Rev. 1985 Oct;87:39–60. doi: 10.1111/j.1600-065x.1985.tb01144.x. [DOI] [PubMed] [Google Scholar]
- Carroll M. C., Fathallah D. M., Bergamaschini L., Alicot E. M., Isenman D. E. Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6868–6872. doi: 10.1073/pnas.87.17.6868. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carroll M. C., Palsdottir A., Belt K. T., Porter R. R. Deletion of complement C4 and steroid 21-hydroxylase genes in the HLA class III region. EMBO J. 1985 Oct;4(10):2547–2552. doi: 10.1002/j.1460-2075.1985.tb03969.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carter R. H., Spycher M. O., Ng Y. C., Hoffman R., Fearon D. T. Synergistic interaction between complement receptor type 2 and membrane IgM on B lymphocytes. J Immunol. 1988 Jul 15;141(2):457–463. [PubMed] [Google Scholar]
- Dodds A. W., Law S. K. Structural basis of the binding specificity of the thioester-containing proteins, C4, C3 and alpha-2-macroglobulin. Complement. 1988;5(2):89–97. doi: 10.1159/000463039. [DOI] [PubMed] [Google Scholar]
- Ellman L., Green I., Judge F., Frank M. M. In vivo studies in C4-deficient guinea pigs. J Exp Med. 1971 Jul 1;134(1):162–175. doi: 10.1084/jem.134.1.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heyman B., Pilström L., Shulman M. J. Complement activation is required for IgM-mediated enhancement of the antibody response. J Exp Med. 1988 Jun 1;167(6):1999–2004. doi: 10.1084/jem.167.6.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heyman B., Wiersma E. J., Kinoshita T. In vivo inhibition of the antibody response by a complement receptor-specific monoclonal antibody. J Exp Med. 1990 Aug 1;172(2):665–668. doi: 10.1084/jem.172.2.665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Isenman D. E., Young J. R. The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. J Immunol. 1984 Jun;132(6):3019–3027. [PubMed] [Google Scholar]
- Law S. K., Dodds A. W., Porter R. R. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J. 1984 Aug;3(8):1819–1823. doi: 10.1002/j.1460-2075.1984.tb02052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsumoto A. K., Kopicky-Burd J., Carter R. H., Tuveson D. A., Tedder T. F., Fearon D. T. Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19. J Exp Med. 1991 Jan 1;173(1):55–64. doi: 10.1084/jem.173.1.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mauff G., Alper C. A., Awdeh Z., Batchelor J. R., Bertrams J., Bruun-Petersen G., Dawkins R. L., Démant P., Edwards J., Grosse-Wilde H. Statement on the nomenclature of human C4 allotypes. Immunobiology. 1983 Mar;164(2):184–191. doi: 10.1016/s0171-2985(83)80009-6. [DOI] [PubMed] [Google Scholar]
- NELSON R. A., Jr The immune-adherence phenomenon; an immunologically specific reaction between microorganisms and erythrocytes leading to enhanced phagocytosis. Science. 1953 Dec 18;118(3077):733–737. doi: 10.1126/science.118.3077.733. [DOI] [PubMed] [Google Scholar]
- Ochs H. D., Wedgwood R. J., Frank M. M., Heller S. R., Hosea S. W. The role of complement in the induction of antibody responses. Clin Exp Immunol. 1983 Jul;53(1):208–216. [PMC free article] [PubMed] [Google Scholar]
- Porter R. R. Complement polymorphism, the major histocompatibility complex and associated diseases: a speculation. Mol Biol Med. 1983 Jul;1(1):161–168. [PubMed] [Google Scholar]
- Reid K. B., Porter R. R. The proteolytic activation systems of complement. Annu Rev Biochem. 1981;50:433–464. doi: 10.1146/annurev.bi.50.070181.002245. [DOI] [PubMed] [Google Scholar]
- Reveille J. D., Arnett F. C., Wilson R. W., Bias W. B., McLean R. H. Null alleles of the fourth component of complement and HLA haplotypes in familial systemic lupus erythematosus. Immunogenetics. 1985;21(4):299–311. doi: 10.1007/BF00430796. [DOI] [PubMed] [Google Scholar]
- Rowe P. C., McLean R. H., Wood R. A., Leggiadro R. J., Winkelstein J. A. Association of homozygous C4B deficiency with bacterial meningitis. J Infect Dis. 1989 Sep;160(3):448–451. doi: 10.1093/infdis/160.3.448. [DOI] [PubMed] [Google Scholar]
- Sandberg A. L., Osler A. G., Shin H. S., Oliveira B. The biologic activities of guinea pig antibodies. II. Modes of complement interaction with gamma 1 and gamma 2-immunoglobulins. J Immunol. 1970 Feb;104(2):329–334. [PubMed] [Google Scholar]
- Schifferli J. A., Ng Y. C., Peters D. K. The role of complement and its receptor in the elimination of immune complexes. N Engl J Med. 1986 Aug 21;315(8):488–495. doi: 10.1056/NEJM198608213150805. [DOI] [PubMed] [Google Scholar]
- Schneider P. M., Carroll M. C., Alper C. A., Rittner C., Whitehead A. S., Yunis E. J., Colten H. R. Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. Restriction fragment length polymorphisms revealing structural deletions, homoduplications, and size variants. J Clin Invest. 1986 Sep;78(3):650–657. doi: 10.1172/JCI112623. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tack B. F. The beta-Cys-gamma-Glu thiolester bond in human C3, C4, and alpha 2-macroglobulin. Springer Semin Immunopathol. 1983;6(4):259–282. doi: 10.1007/BF02116276. [DOI] [PubMed] [Google Scholar]
- Yu C. Y., Campbell R. D. Definitive RFLPs to distinguish between the human complement C4A/C4B isotypes and the major Rodgers/Chido determinants: application to the study of C4 null alleles. Immunogenetics. 1987;25(6):383–390. doi: 10.1007/BF00396104. [DOI] [PubMed] [Google Scholar]