Abstract
We have isolated C3bR from surface-labeled erythrocytes of 180 normal individuals and 45 patients with SLE. These studies have identified a previously unrecognized C3bR molecule on E with a Mr of approximately 160,000 daltons on nonreduced SDS-polyacrylamide gels. A similar receptor phenotype is also found on other C3bR-bearing peripheral blood leukocytes. Family studies demonstrate that this approximately 160,000- dalton molecule represents a third allele that is inherited in a codominant fashion at the same locus as the two previously described C3bR alleles. In unrelated normal donors a common allele (A) determines an approximately 190,000-dalton C3bR (gene frequency 0.83), a second allele (B) determines an approximately 220,000-dalton C3bR (gene frequency = 0.16), and a third rare allele (C) determines an approximately 160,000-dalton C3bR (gene frequency = 0.01). There were no major differences in gene frequencies among Caucasians and blacks or normal individuals and patients with SLE. However, compared with normal individuals, heterozygous C3bR-AC patients with SLE express large amounts of the approximately 160,000-dalton C3bR on E. Expression of C3bR molecules among heterozygous siblings is similar, suggesting that an inherited factor controls expression of the two molecules in heterozygous donors. These observations constitute an instructive example of a structural polymorphism of an integral membrane glycoprotein and provide a structural and genetic basis for further molecular and functional analyses of C3bR in normal and patient populations.
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- Atkinson J. P., McGinnis K., Brown L., Peterein J., Shreffler D. A murine C4 molecule with reduced hemolytic efficiency. J Exp Med. 1980 Feb 1;151(2):492–497. doi: 10.1084/jem.151.2.492. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- Dobson N. J., Lambris J. D., Ross G. D. Characteristics of isolated erythrocyte complement receptor type one (CR1, C4b-C3b receptor) and CR1-specific antibodies. J Immunol. 1981 Feb;126(2):693–698. [PubMed] [Google Scholar]
- Dykman T. R., Cole J. L., Iida K., Atkinson J. P. Polymorphism of human erythrocyte C3b/C4b receptor. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1698–1702. doi: 10.1073/pnas.80.6.1698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dykman T. R., Cole J. L., Iida K., Atkinson J. P. Structural heterogeneity of the C3b/C4b receptor (Cr 1) on human peripheral blood cells. J Exp Med. 1983 Jun 1;157(6):2160–2165. doi: 10.1084/jem.157.6.2160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon D. T. Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte. J Exp Med. 1980 Jul 1;152(1):20–30. doi: 10.1084/jem.152.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fearon D. T. Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5867–5871. doi: 10.1073/pnas.76.11.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iida K., Mornaghi R., Nussenzweig V. Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus. J Exp Med. 1982 May 1;155(5):1427–1438. doi: 10.1084/jem.155.5.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson D. C., Spear P. G. O-linked oligosaccharides are acquired by herpes simplex virus glycoproteins in the Golgi apparatus. Cell. 1983 Mar;32(3):987–997. doi: 10.1016/0092-8674(83)90083-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kessler S. W. Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A. J Immunol. 1975 Dec;115(6):1617–1624. [PubMed] [Google Scholar]
- Kulczycki A., Jr, Krause V., Killion C. C., Atkinson J. P. Improved cell surface radioiodination of macrophages. J Immunol Methods. 1980;37(2):133–138. doi: 10.1016/0022-1759(80)90198-2. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Roos M. H., Atkinson J. P., Shreffler D. C. Molecular characterization of the Ss and Slp (C4) proteins of the mouse H-2 complex: subunit composition, chain size polymorphism, and an intracellular (PRO-Ss) precursor. J Immunol. 1978 Sep;121(3):1106–1115. [PubMed] [Google Scholar]
- Tan E. M., Cohen A. S., Fries J. F., Masi A. T., McShane D. J., Rothfield N. F., Schaller J. G., Talal N., Winchester R. J. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. doi: 10.1002/art.1780251101. [DOI] [PubMed] [Google Scholar]
- Wilson J. G., Wong W. W., Schur P. H., Fearon D. T. Mode of inheritance of decreased C3b receptors on erythrocytes of patients with systemic lupus erythematosus. N Engl J Med. 1982 Oct 14;307(16):981–986. doi: 10.1056/NEJM198210143071604. [DOI] [PubMed] [Google Scholar]
- Wong W. W., Wilson J. G., Fearon D. T. Genetic regulation of a structural polymorphism of human C3b receptor. J Clin Invest. 1983 Aug;72(2):685–693. doi: 10.1172/JCI111018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- von Zabern I., Gigli I. Conformational changes in complement component C4 induced by activation, treatment with amines, chaotropes, or freezing-thawing, detectable by radioiodination using lactoperoxidase. J Immunol. 1982 Mar;128(3):1439–1442. [PubMed] [Google Scholar]