Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 Jul 1;164(1):50–59. doi: 10.1084/jem.164.1.50

Identification of a restriction fragment length polymorphism by a CR1 cDNA that correlates with the number of CR1 on erythrocytes

PMCID: PMC2188187  PMID: 3014040

Abstract

A genetic basis for the regulation of the number of CR1 on E of different normal individuals was investigated by probing Southern blots of their genomic DNA with a 0.75-kb fragment of CR1 cDNA. Using Hind III, we observed a RFLP involving fragments of 7.4 kb and 6.9 kb that correlated with the number of CR1 on E. 32 individuals having only the 7.4-kb restriction fragment had a mean of 661 +/- 33 (SEM) CR1/E, 11 donors having both restriction fragments had a mean of 455 +/- 52 CR1/E, and 7 individuals having only the 6.9-kb fragment had a mean of 156 +/- 13 CR1/E, all means being significantly different (p less than 0.005). Cosegregation in a normal family of the Hind III restriction fragments with the S, F, and F' structural allotypes of CR1 confirmed that the regulatory element identified by these fragments is linked to the CR1 gene. Moreover, an analysis of the relative expression on E of these structural allotypes in association with either the 7.4-kb Hind III fragment or the 6.9-kb fragment showed that this regulatory element is cis-acting. In contrast, quantitation of CR1 of B lymphocytes and neutrophils revealed no differences in total CR1 expression between individuals homozygous for the 7.4-kb and 6.9-kb Hind III fragments. Thus, we have identified a genomic polymorphism that is linked to the CR1 gene and is associated with a cis-acting regulatory element for the expression of CR1 on E.

Full Text

The Full Text of this article is available as a PDF (1,022.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnaout M. A., Melamed J., Tack B. F., Colten H. R. Characterization of the human complement (c3b) receptor with a fluid phase C3b dimer. J Immunol. 1981 Oct;127(4):1348–1354. [PubMed] [Google Scholar]
  2. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  3. Changelian P. S., Jack R. M., Collins L. A., Fearon D. T. PMA induces the ligand-independent internalization of CR1 on human neutrophils. J Immunol. 1985 Mar;134(3):1851–1858. [PubMed] [Google Scholar]
  4. Cornacoff J. B., Hebert L. A., Smead W. L., VanAman M. E., Birmingham D. J., Waxman F. J. Primate erythrocyte-immune complex-clearing mechanism. J Clin Invest. 1983 Feb;71(2):236–247. doi: 10.1172/JCI110764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Darnell J. E., Jr Variety in the level of gene control in eukaryotic cells. Nature. 1982 Jun 3;297(5865):365–371. doi: 10.1038/297365a0. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Dykman T. R., Hatch J. A., Aqua M. S., Atkinson J. P. Polymorphism of the C3b/C4b receptor (CR1): characterization of a fourth allele. J Immunol. 1985 Mar;134(3):1787–1789. [PubMed] [Google Scholar]
  9. Dykman T. R., Hatch J. A., Atkinson J. P. Polymorphism of the human C3b/C4b receptor. Identification of a third allele and analysis of receptor phenotypes in families and patients with systemic lupus erythematosus. J Exp Med. 1984 Mar 1;159(3):691–703. doi: 10.1084/jem.159.3.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Fearon D. T., Wong W. W. Complement ligand-receptor interactions that mediate biological responses. Annu Rev Immunol. 1983;1:243–271. doi: 10.1146/annurev.iy.01.040183.001331. [DOI] [PubMed] [Google Scholar]
  12. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  13. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Lehrman M. A., Schneider W. J., Südhof T. C., Brown M. S., Goldstein J. L., Russell D. W. Mutation in LDL receptor: Alu-Alu recombination deletes exons encoding transmembrane and cytoplasmic domains. Science. 1985 Jan 11;227(4683):140–146. doi: 10.1126/science.3155573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Medof M. E., Iida K., Mold C., Nussenzweig V. Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes. J Exp Med. 1982 Dec 1;156(6):1739–1754. doi: 10.1084/jem.156.6.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Minota S., Terai C., Nojima Y., Takano K., Takai E., Miyakawa Y., Takaku F. Low C3b receptor reactivity on erythrocytes from patients with systemic lupus erythematosus detected by immune adherence hemagglutination and radioimmunoassays with monoclonal antibody. Arthritis Rheum. 1984 Dec;27(12):1329–1335. doi: 10.1002/art.1780271202. [DOI] [PubMed] [Google Scholar]
  18. Miyakawa Y., Yamada A., Kosaka K., Tsuda F., Kosugi E., Mayumi M. Defective immune-adherence (C3b) receptor on erythrocytes from patients with systemic lupus erythematosus. Lancet. 1981 Sep 5;2(8245):493–497. doi: 10.1016/s0140-6736(81)90882-5. [DOI] [PubMed] [Google Scholar]
  19. NISONOFF A. ENZYMATIC DIGESTION OF RABBIT GAMMA GLOBULIN AND ANTIBODY AND CHROMATOGRAPHY OF DIGESTION PRODUCTS. Methods Med Res. 1964;10:134–141. [PubMed] [Google Scholar]
  20. Nadler L. M., Stashenko P., Hardy R., van Agthoven A., Terhorst C., Schlossman S. F. Characterization of a human B cell-specific antigen (B2) distinct from B1. J Immunol. 1981 May;126(5):1941–1947. [PubMed] [Google Scholar]
  21. Neuberger M. S. Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells. EMBO J. 1983;2(8):1373–1378. doi: 10.1002/j.1460-2075.1983.tb01594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  23. Reynes M., Aubert J. P., Cohen J. H., Audouin J., Tricottet V., Diebold J., Kazatchkine M. D. Human follicular dendritic cells express CR1, CR2, and CR3 complement receptor antigens. J Immunol. 1985 Oct;135(4):2687–2694. [PubMed] [Google Scholar]
  24. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  25. Unkeless J. C., Healey G. A. Quantitation of proteins and internal antigen pools by a monoclonal sandwich radioimmune assay. J Immunol Methods. 1983;56(1):1–11. doi: 10.1016/0022-1759(83)90043-1. [DOI] [PubMed] [Google Scholar]
  26. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Wong W. W., Klickstein L. B., Smith J. A., Weis J. H., Fearon D. T. Identification of a partial cDNA clone for the human receptor for complement fragments C3b/C4b. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7711–7715. doi: 10.1073/pnas.82.22.7711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Yoon S. H., Fearon D. T. Characterization of a soluble form of the C3b/C4b receptor (CR1) in human plasma. J Immunol. 1985 May;134(5):3332–3338. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES