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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Aug;93(2):195–199. doi: 10.1111/j.1365-2249.1993.tb07965.x

Determination of soluble CD21 as a parameter of B cell activation.

H P Huemer 1, C Larcher 1, W M Prodinger 1, A L Petzer 1, M Mitterer 1, N Falser 1
PMCID: PMC1554846  PMID: 8348744

Abstract

In this study we established a novel solid-phase immunoassay for CD21 using the time-resolved fluorescence of lanthanide chelates. The capture assay was able to detect concentrations of as low as 100 pg of CD21 antigen per millilitre of sample and was used for quantitative determination of CD21 in lysates of different cell lines as well as in patient serum specimens. CD21 was measured in lysates of tonsils and cell lines of B, T cell and myelomonocyte lineage, and appeared to consist of monomeric antigen under the detergent conditions used. Elevated levels of soluble CD21 were observed in serum of patients with Epstein-Barr virus (EBV) infection, a disease known to be associated with polyclonal B cell activation, and in infection with the lymphotropic rubella virus. Significantly increased levels were also found in malignancies which are associated with EBV. In patients with nasopharyngeal carcinoma (NPC), a correlation with the titre of EBV-specific IgA was observed, thus supporting a possible role of soluble CD21 as a marker for disease activity in certain malignancies. Our data suggest that measurement of soluble CD21 could serve as a marker for activation of the immune system and diseases involving the B cell lymphoid system. Possible mechanisms and functions of soluble CD21 are discussed.

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Selected References

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  1. Aubry J. P., Pochon S., Graber P., Jansen K. U., Bonnefoy J. Y. CD21 is a ligand for CD23 and regulates IgE production. Nature. 1992 Aug 6;358(6386):505–507. doi: 10.1038/358505a0. [DOI] [PubMed] [Google Scholar]
  2. Bohnsack J. F., Cooper N. R. CR2 ligands modulate human B cell activation. J Immunol. 1988 Oct 15;141(8):2569–2576. [PubMed] [Google Scholar]
  3. Carel J. C., Myones B. L., Frazier B., Holers V. M. Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection. J Biol Chem. 1990 Jul 25;265(21):12293–12299. [PubMed] [Google Scholar]
  4. Chain B. M., Bou-Gharios G., Olsen I. Endopeptidase activities associated with the plasma membrane compartment of an antigen-presenting B cell. Clin Exp Immunol. 1989 Jan;75(1):87–92. [PMC free article] [PubMed] [Google Scholar]
  5. Erdei A., Melchers F., Schulz T., Dierich M. The action of human C3 in soluble or cross-linked form with resting and activated murine B lymphocytes. Eur J Immunol. 1985 Feb;15(2):184–188. doi: 10.1002/eji.1830150214. [DOI] [PubMed] [Google Scholar]
  6. Fingeroth J. D., Weis J. J., Tedder T. F., Strominger J. L., Biro P. A., Fearon D. T. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510–4514. doi: 10.1073/pnas.81.14.4510. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fischer E., Delibrias C., Kazatchkine M. D. Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes. J Immunol. 1991 Feb 1;146(3):865–869. [PubMed] [Google Scholar]
  8. Frade R., Crevon M. C., Barel M., Vazquez A., Krikorian L., Charriaut C., Galanaud P. Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp 140 molecule. Eur J Immunol. 1985 Jan;15(1):73–76. doi: 10.1002/eji.1830150114. [DOI] [PubMed] [Google Scholar]
  9. Hartmann K. U., Bokisch V. A. Stimulation of murine B lymphocytes by isolated C3b. J Exp Med. 1975 Sep 1;142(3):600–610. doi: 10.1084/jem.142.3.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hatzfeld A., Fischer E., Levesque J. P., Perrin R., Hatzfeld J., Kazatchkine M. D. Binding of C3 and C3dg to the CR2 complement receptor induces growth of an Epstein-Barr virus-positive human B cell line. J Immunol. 1988 Jan 1;140(1):170–175. [PubMed] [Google Scholar]
  11. Hebell T., Ahearn J. M., Fearon D. T. Suppression of the immune response by a soluble complement receptor of B lymphocytes. Science. 1991 Oct 4;254(5028):102–105. doi: 10.1126/science.1718035. [DOI] [PubMed] [Google Scholar]
  12. Iida K., Nadler L., Nussenzweig V. Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody. J Exp Med. 1983 Oct 1;158(4):1021–1033. doi: 10.1084/jem.158.4.1021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koizumi S., Zhang X. K., Imai S., Sugiura M., Usui N., Osato T. Infection of the HTLV-I-harbouring T-lymphoblastoid line MT-2 by Epstein-Barr virus. Virology. 1992 Jun;188(2):859–863. doi: 10.1016/0042-6822(92)90542-w. [DOI] [PubMed] [Google Scholar]
  14. Lambris J. D., Dobson N. J., Ross G. D. Isolation of lymphocyte membrane complement receptor type two (the C3d receptor) and preparation of receptor-specific antibody. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1828–1832. doi: 10.1073/pnas.78.3.1828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ling N. R., Brown B. Properties of soluble CR2 in human serum. Immunobiology. 1992 Aug;185(2-4):403–414. doi: 10.1016/S0171-2985(11)80656-X. [DOI] [PubMed] [Google Scholar]
  16. Ling N., Hansel T., Richardson P., Brown B. Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia. Clin Exp Immunol. 1991 Apr;84(1):16–22. doi: 10.1111/j.1365-2249.1991.tb08117.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lobo P. I., Burge J. J. In vitro studies on the immune regulatory role of complement receptors (C3) present on human B lymphocytes. Eur J Immunol. 1982 Aug;12(8):682–686. doi: 10.1002/eji.1830120811. [DOI] [PubMed] [Google Scholar]
  18. Lowe J., Brown B., Hardie D., Richardson P., Ling N. Soluble forms of CD21 and CD23 antigens in the serum in B cell chronic lymphocytic leukaemia. Immunol Lett. 1989 Jan 31;20(2):103–109. doi: 10.1016/0165-2478(89)90093-x. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Meuth J. L., Morgan E. L., DiSipio R. G., Hugli T. E. Suppression of T lymphocyte functions by human C3 fragments. I. Inhibition of human T cell proliferative responses by a kallikrein cleavage fragment of human iC3b. J Immunol. 1983 Jun;130(6):2605–2611. [PubMed] [Google Scholar]
  21. Misasi R., Huemer H. P., Schwaeble W., Sölder E., Larcher C., Dierich M. P. Human complement factor H: an additional gene product of 43 kDa isolated from human plasma shows cofactor activity for the cleavage of the third component of complement. Eur J Immunol. 1989 Sep;19(9):1765–1768. doi: 10.1002/eji.1830190936. [DOI] [PubMed] [Google Scholar]
  22. Mukkala V. M., Mikola H., Hemmilä I. The synthesis and use of activated N-benzyl derivatives of diethylenetriaminetetraacetic acids: alternative reagents for labeling of antibodies with metal ions. Anal Biochem. 1989 Feb 1;176(2):319–325. doi: 10.1016/0003-2697(89)90316-3. [DOI] [PubMed] [Google Scholar]
  23. Myones B. L., Ross G. D. Identification of a spontaneously shed fragment of B cell complement receptor type two (CR2) containing the C3d-binding site. Complement. 1987;4(2):87–98. doi: 10.1159/000463012. [DOI] [PubMed] [Google Scholar]
  24. Nemerow G. R., McNaughton M. E., Cooper N. R. Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes. J Immunol. 1985 Nov;135(5):3068–3073. [PubMed] [Google Scholar]
  25. Nemerow G. R., Wolfert R., McNaughton M. E., Cooper N. R. Identification and characterization of the Epstein-Barr virus receptor on human B lymphocytes and its relationship to the C3d complement receptor (CR2). J Virol. 1985 Aug;55(2):347–351. doi: 10.1128/jvi.55.2.347-351.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Petzer A. L., Schulz T. F., Stauder R., Eigentler A., Myones B. L., Dierich M. P. Structural and functional analysis of CR2/EBV receptor by means of monoclonal antibodies and limited tryptic digestion. Immunology. 1988 Jan;63(1):47–53. [PMC free article] [PubMed] [Google Scholar]
  27. Ross G. D., Polley M. J., Rabellino E. M., Grey H. M. Two different complement receptors on human lymphocytes. One specific for C3b and one specific for C3b inactivator-cleaved C3b. J Exp Med. 1973 Oct 1;138(4):798–811. doi: 10.1084/jem.138.4.798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rothlein R., Mainolfi E. A., Czajkowski M., Marlin S. D. A form of circulating ICAM-1 in human serum. J Immunol. 1991 Dec 1;147(11):3788–3793. [PubMed] [Google Scholar]
  29. Sarfati M., Bron D., Lagneaux L., Fonteyn C., Frost H., Delespesse G. Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia. Blood. 1988 Jan;71(1):94–98. [PubMed] [Google Scholar]
  30. Schenkein H. A., Genco R. J. Inhibition of lymphocyte blastogenesis by C3c and C3d. J Immunol. 1979 Mar;122(3):1126–1133. [PubMed] [Google Scholar]
  31. Sixbey J. W., Lemon S. M., Pagano J. S. A second site for Epstein-Barr virus shedding: the uterine cervix. Lancet. 1986 Nov 15;2(8516):1122–1124. doi: 10.1016/s0140-6736(86)90531-3. [DOI] [PubMed] [Google Scholar]
  32. Soini E., Kojola H. Time-resolved fluorometer for lanthanide chelates--a new generation of nonisotopic immunoassays. Clin Chem. 1983 Jan;29(1):65–68. [PubMed] [Google Scholar]
  33. Symons J. A., Duff G. W. A soluble form of the interleukin-1 receptor produced by a human B cell line. FEBS Lett. 1990 Oct 15;272(1-2):133–136. doi: 10.1016/0014-5793(90)80466-v. [DOI] [PubMed] [Google Scholar]
  34. Tsoukas C. D., Lambris J. D. Expression of CR2/EBV receptors on human thymocytes detected by monoclonal antibodies. Eur J Immunol. 1988 Aug;18(8):1299–1302. doi: 10.1002/eji.1830180823. [DOI] [PubMed] [Google Scholar]
  35. Weis J. J., Tedder T. F., Fearon D. T. Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. Proc Natl Acad Sci U S A. 1984 Feb;81(3):881–885. doi: 10.1073/pnas.81.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wilson B. S., Platt J. L., Kay N. E. Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro. Blood. 1985 Oct;66(4):824–829. [PubMed] [Google Scholar]
  37. Yanagihara Y., Sarfati M., Marsh D., Nutman T., Delespesse G. Serum levels of IgE-binding factor (soluble CD23) in diseases associated with elevated IgE. Clin Exp Allergy. 1990 Jul;20(4):395–401. doi: 10.1111/j.1365-2222.1990.tb02800.x. [DOI] [PubMed] [Google Scholar]
  38. Young L. S., Clark D., Sixbey J. W., Rickinson A. B. Epstein-Barr virus receptors on human pharyngeal epithelia. Lancet. 1986 Feb 1;1(8475):240–242. doi: 10.1016/s0140-6736(86)90776-2. [DOI] [PubMed] [Google Scholar]

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