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. 1990 Sep 1;172(3):693–700. doi: 10.1084/jem.172.3.693

Mechanism of formation of human IgE-binding factors (soluble CD23): III. Evidence for a receptor (Fc epsilon RII)-associated proteolytic activity

PMCID: PMC2188566  PMID: 2143772

Abstract

There is mounting evidence that Fc epsilon RII (CD23) and its soluble fragments (IgE-binding factors [BFs] or soluble CD23) have pleiotropic activities. IgE-BFs are formed mainly by the proteolytic cleavage of surface Fc epsilon RII; they are first released as 37- and 33-kD unstable molecules that are subsequently transformed into 25-kD IgE- BFs. In this study, purified and radioiodinated 37-kD IgE-BFs as well as 45-kD Fc epsilon RII were used as substrates to identify the proteases leading to the formation of 25-kD IgE-BFs. These substrates generate 25-kD IgE-BFs when incubated with several Fc epsilon RII- bearing cells, including CHO1-7 cells (transfected with Fc epsilon RII cDNA); by contrast Fc epsilon RII- cells, including CHO control cells, have no effect. Highly purified unlabeled native 37-kD and recombinant 29-kD IgE-BFs also cleave labeled 45-kD Fc epsilon RII into 25-kD IgE- BFs. The proteolytic activity of these purified IgE-BFs is specifically removed by immunoprecipitation with an antibody against IgE-BFs. These data strongly suggest that Fc epsilon RII and some of its soluble fragments play an active role in the proteolytic mechanism generating IgE-BFs. They are supported by the observation that IgE-BFs released by CHO1-7 cells are cleaved exactly at the same sites as B cell-derived IgE-BFs. Taken collectively, the results are compatible with an autoproteolytic process.

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Selected References

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  1. Amoscato A. A., Alexander J. W., Babcock G. F. Surface aminopeptidase activity of human lymphocytes. I. Biochemical and biologic properties of intact cells. J Immunol. 1989 Feb 15;142(4):1245–1252. [PubMed] [Google Scholar]
  2. Armitage R. J., Goff L. K., Beverley P. C. Expression and functional role of CD23 on T cells. Eur J Immunol. 1989 Jan;19(1):31–35. doi: 10.1002/eji.1830190106. [DOI] [PubMed] [Google Scholar]
  3. Armitage R. J., Goff L. K. Functional interaction between B cell subpopulations defined by CD23 expression. Eur J Immunol. 1988 Nov;18(11):1753–1760. doi: 10.1002/eji.1830181115. [DOI] [PubMed] [Google Scholar]
  4. Asselbergs F. A., Will H., Wingfield P., Hirschi M. A recombinant Chinese hamster ovary cell line containing a 300-fold amplified tetramer of the hepatitis B genome together with a double selection marker expresses high levels of viral protein. J Mol Biol. 1986 Jun 5;189(3):401–411. doi: 10.1016/0022-2836(86)90312-8. [DOI] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  6. Bonnefoy J. Y., Aubry J. P., Peronne C., Wijdenes J., Banchereau J. Production and characterization of a monoclonal antibody specific for the human lymphocyte low affinity receptor for IgE: CD 23 is a low affinity receptor for IgE. J Immunol. 1987 May 1;138(9):2970–2978. [PubMed] [Google Scholar]
  7. Burckhardt S. E., Woodgate R., Scheuermann R. H., Echols H. UmuD mutagenesis protein of Escherichia coli: overproduction, purification, and cleavage by RecA. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1811–1815. doi: 10.1073/pnas.85.6.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Capron A., Dessaint J. P., Capron M., Ouma J. H., Butterworth A. E. Immunity to schistosomes: progress toward vaccine. Science. 1987 Nov 20;238(4830):1065–1072. doi: 10.1126/science.3317823. [DOI] [PubMed] [Google Scholar]
  9. Dorsch-Häsler K., Keil G. M., Weber F., Jasin M., Schaffner W., Koszinowski U. H. A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8325–8329. doi: 10.1073/pnas.82.24.8325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Flores-Romo L., Cairns J. A., Millsum M. J., Gordon J. Soluble fragments of the low-affinity IgE receptor (CD23) inhibit the spontaneous migration of U937 monocytic cells: neutralization of MIF-activity by a CD23 antibody. Immunology. 1989 Aug;67(4):547–549. [PMC free article] [PubMed] [Google Scholar]
  11. Giam C. Z., Boros I. In vivo and in vitro autoprocessing of human immunodeficiency virus protease expressed in Escherichia coli. J Biol Chem. 1988 Oct 15;263(29):14617–14620. [PubMed] [Google Scholar]
  12. Gordon J., Cairns J. A., Millsum M. J., Gillis S., Guy G. R. Interleukin 4 and soluble CD23 as progression factors for human B lymphocytes: analysis of their interactions with agonists of the phosphoinositide "dual pathway" of signalling. Eur J Immunol. 1988 Oct;18(10):1561–1565. doi: 10.1002/eji.1830181014. [DOI] [PubMed] [Google Scholar]
  13. Grant G. A., Eisen A. Z., Marmer B. L., Roswit W. T., Goldberg G. I. The activation of human skin fibroblast procollagenase. Sequence identification of the major conversion products. J Biol Chem. 1987 Apr 25;262(12):5886–5889. [PubMed] [Google Scholar]
  14. Guy G. R., Gordon J. Coordinated action of IgE and a B-cell-stimulatory factor on the CD23 receptor molecule up-regulates B-lymphocyte growth. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6239–6243. doi: 10.1073/pnas.84.17.6239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ikuta K., Takami M., Kim C. W., Honjo T., Miyoshi T., Tagaya Y., Kawabe T., Yodoi J. Human lymphocyte Fc receptor for IgE: sequence homology of its cloned cDNA with animal lectins. Proc Natl Acad Sci U S A. 1987 Feb;84(3):819–823. doi: 10.1073/pnas.84.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kehry M. R., Yamashita L. C. Low-affinity IgE receptor (CD23) function on mouse B cells: role in IgE-dependent antigen focusing. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7556–7560. doi: 10.1073/pnas.86.19.7556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kikutani H., Inui S., Sato R., Barsumian E. L., Owaki H., Yamasaki K., Kaisho T., Uchibayashi N., Hardy R. R., Hirano T. Molecular structure of human lymphocyte receptor for immunoglobulin E. Cell. 1986 Dec 5;47(5):657–665. doi: 10.1016/0092-8674(86)90508-8. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Lazure C., Seidah N. G., Chrétien M., Lallier R., St-Pierre S. Primary structure determination of Escherichia coli heat-stable enterotoxin of porcine origin. Can J Biochem Cell Biol. 1983 May;61(5):287–292. doi: 10.1139/o83-039. [DOI] [PubMed] [Google Scholar]
  20. Lee B. W., Simmons C. F., Jr, Wileman T., Geha R. S. Intracellular cleavage of newly synthesized low affinity Fc epsilon receptor (Fc epsilon R2) provides a second pathway for the generation of the 28-kDa soluble Fc epsilon R2 fragment. J Immunol. 1989 Mar 1;142(5):1614–1620. [PubMed] [Google Scholar]
  21. Legendre J. L., Jones H. P. Purification and characterization of calpain from human polymorphonuclear leukocytes. Inflammation. 1988 Feb;12(1):51–65. doi: 10.1007/BF00915892. [DOI] [PubMed] [Google Scholar]
  22. Letellier M., Nakajima T., Delespesse G. IgE receptor on human lymphocytes. IV. Further analysis of its structure and of the role of N-linked carbohydrates. J Immunol. 1988 Oct 1;141(7):2374–2381. [PubMed] [Google Scholar]
  23. Letellier M., Sarfati M., Delespesse G. Mechanisms of formation of IgE-binding factors (soluble CD23)--I. Fc epsilon R II bearing B cells generate IgE-binding factors of different molecular weights. Mol Immunol. 1989 Dec;26(12):1105–1112. doi: 10.1016/0161-5890(89)90054-0. [DOI] [PubMed] [Google Scholar]
  24. Lüdin C., Hofstetter H., Sarfati M., Levy C. A., Suter U., Alaimo D., Kilchherr E., Frost H., Delespesse G. Cloning and expression of the cDNA coding for a human lymphocyte IgE receptor. EMBO J. 1987 Jan;6(1):109–114. doi: 10.1002/j.1460-2075.1987.tb04726.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meinke G. C., Magro A. M., Lawrence D. A., Spiegelberg H. L. Characterization of an IgE receptor isolated from cultured B-type lymphoblastoid cells. J Immunol. 1978 Oct;121(4):1321–1328. [PubMed] [Google Scholar]
  26. Mentlein R., Heymann E., Scholz W., Feller A. C., Flad H. D. Dipeptidyl peptidase IV as a new surface marker for a subpopulation of human T-lymphocytes. Cell Immunol. 1984 Nov;89(1):11–19. doi: 10.1016/0008-8749(84)90192-8. [DOI] [PubMed] [Google Scholar]
  27. Morelli A., Grasso M., Meloni T., Forteleoni G., Zocchi E., De Flora A. Favism: impairment of proteolytic systems in red blood cells. Blood. 1987 Jun;69(6):1753–1758. [PubMed] [Google Scholar]
  28. Mossalayi M. D., Lecron J. C., Dalloul A. H., Sarfati M., Bertho J. M., Hofstetter H., Delespesse G., Debre P. Soluble CD23 (Fc epsilon RII) and interleukin 1 synergistically induce early human thymocyte maturation. J Exp Med. 1990 Mar 1;171(3):959–964. doi: 10.1084/jem.171.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nakajima T., Delespesse G. IgE receptors on human lymphocytes. I. Identification of the molecules binding to monoclonal anti-Fc epsilon receptor antibodies. Eur J Immunol. 1986 Jul;16(7):809–814. doi: 10.1002/eji.1830160715. [DOI] [PubMed] [Google Scholar]
  30. Nakajima T., Sarfati M., Delespesse G. Relationship between human IgE-binding factors (IgE-BF) and lymphocyte receptors for IgE. J Immunol. 1987 Aug 1;139(3):848–854. [PubMed] [Google Scholar]
  31. Nishimura Y., Higaki M., Kato K. Identification of a precursor form of cathepsin D in microsomal lumen: characterization of enzymatic activation and proteolytic. Biochem Biophys Res Commun. 1987 Oct 14;148(1):335–343. doi: 10.1016/0006-291x(87)91115-6. [DOI] [PubMed] [Google Scholar]
  32. Peterson L. H., Conrad D. H. Fine specificity, structure, and proteolytic susceptibility of the human lymphocyte receptor for IgE. J Immunol. 1985 Oct;135(4):2654–2660. [PubMed] [Google Scholar]
  33. Pène J., Rousset F., Brière F., Chrétien I., Wideman J., Bonnefoy J. Y., De Vries J. E. Interleukin 5 enhances interleukin 4-induced IgE production by normal human B cells. The role of soluble CD23 antigen. Eur J Immunol. 1988 Jun;18(6):929–935. doi: 10.1002/eji.1830180615. [DOI] [PubMed] [Google Scholar]
  34. Rector E., Nakajima T., Rocha C., Duncan D., Lestourgeon D., Mitchell R. S., Fischer J., Sehon A. H., Delespesse G. Detection and characterization of monoclonal antibodies specific to IgE receptors on human lymphocytes by flow cytometry. Immunology. 1985 Jul;55(3):481–488. [PMC free article] [PubMed] [Google Scholar]
  35. Richards O. C., Ivanoff L. A., Bienkowska-Szewczyk K., Butt B., Petteway S. R., Jr, Rothstein M. A., Ehrenfeld E. Formation of poliovirus RNA polymerase 3D in Escherichia coli by cleavage of fusion proteins expressed from cloned viral cDNA. Virology. 1987 Dec;161(2):348–356. doi: 10.1016/0042-6822(87)90127-9. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Sarfati M., Delespesse G. Possible role of human lymphocyte receptor for IgE (CD23) or its soluble fragments in the in vitro synthesis of human IgE. J Immunol. 1988 Oct 1;141(7):2195–2199. [PubMed] [Google Scholar]
  38. Sarfati M., Nakajima T., Frost H., Kilccherr E., Delespesse G. Purification and partial biochemical characterization of IgE-binding factors secreted by a human B lymphoblastoid cell line. Immunology. 1987 Apr;60(4):539–545. [PMC free article] [PubMed] [Google Scholar]
  39. Sarfati M., Nutman T., Fonteyn C., Delespesse G. Presence of antigenic determinants common to Fc IgE receptors on human macrophages, T and B lymphocytes and IgE-binding factors. Immunology. 1986 Dec;59(4):569–575. [PMC free article] [PubMed] [Google Scholar]
  40. Sarfati M., Rector E., Rubio-Trujillo M., Wong K., Sehon A. H., Delespesse G. In vitro synthesis of IgE by human lymphocytes. III. IgE-potentiating activity of culture supernatants from Epstein-Barr virus (EBV) transformed B cells. Immunology. 1984 Oct;53(2):207–214. [PMC free article] [PubMed] [Google Scholar]
  41. Sarfati M., Rector E., Wong K., Rubio-Trujillo M., Sehon A. H., Delespesse G. In vitro synthesis of IgE by human lymphocytes. II. Enhancement of the spontaneous IgE synthesis by IgE-binding factors secreted by RPMI 8866 lymphoblastoid B cells. Immunology. 1984 Oct;53(2):197–205. [PMC free article] [PubMed] [Google Scholar]
  42. Shipp M. A., Vijayaraghavan J., Schmidt E. V., Masteller E. L., D'Adamio L., Hersh L. B., Reinherz E. L. Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. Proc Natl Acad Sci U S A. 1989 Jan;86(1):297–301. doi: 10.1073/pnas.86.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Slilaty S. N., Rupley J. A., Little J. W. Intramolecular cleavage of LexA and phage lambda repressors: dependence of kinetics on repressor concentration, pH, temperature, and solvent. Biochemistry. 1986 Nov 4;25(22):6866–6875. doi: 10.1021/bi00370a020. [DOI] [PubMed] [Google Scholar]
  44. Swendeman S., Thorley-Lawson D. A. The activation antigen BLAST-2, when shed, is an autocrine BCGF for normal and transformed B cells. EMBO J. 1987 Jun;6(6):1637–1642. doi: 10.1002/j.1460-2075.1987.tb02412.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Thorley-Lawson D. A., Swendeman S. L., Edson C. M. Biochemical analysis suggests distinct functional roles for the BLAST-1 and BLAST-2 antigens. J Immunol. 1986 Mar 1;136(5):1745–1751. [PubMed] [Google Scholar]
  46. Yukawa K., Kikutani H., Owaki H., Yamasaki K., Yokota A., Nakamura H., Barsumian E. L., Hardy R. R., Suemura M., Kishimoto T. A B cell-specific differentiation antigen, CD23, is a receptor for IgE (Fc epsilon R) on lymphocytes. J Immunol. 1987 Apr 15;138(8):2576–2580. [PubMed] [Google Scholar]
  47. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]

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