Determination of soluble CD21 as a parameter of B cell activation

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.

[1]  J. Bonnefoy,et al.  CD21 is a ligand for CD23 and regulates IgE production , 1992, Nature.

[2]  N. Ling,et al.  Properties of soluble CR2 in human serum. , 1992, Immunobiology.

[3]  T. Osato,et al.  Infection of the HTLV-I-harbouring T-lymphoblastoid line MT-2 by Epstein-Barr virus. , 1992, Virology.

[4]  R. Rothlein,et al.  A form of circulating ICAM-1 in human serum. , 1991, Journal of immunology.

[5]  D. Fearon,et al.  Suppression of the immune response by a soluble complement receptor of B lymphocytes. , 1991, Science.

[6]  N. Ling,et al.  Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia , 1991, Clinical and experimental immunology.

[7]  M. Kazatchkine,et al.  Expression of CR2 (the C3dg/EBV receptor, CD21) on normal human peripheral blood T lymphocytes. , 1991, Journal of immunology.

[8]  D. Tuveson,et al.  Intersection of the complement and immune systems: a signal transduction complex of the B lymphocyte-containing complement receptor type 2 and CD19 , 1991, The Journal of experimental medicine.

[9]  G. Duff,et al.  A soluble form of the interleukin‐1 receptor produced by a human B cell line , 1990, FEBS letters.

[10]  B. Myones,et al.  Structural requirements for C3d,g/Epstein-Barr virus receptor (CR2/CD21) ligand binding, internalization, and viral infection. , 1990, The Journal of biological chemistry.

[11]  T. Nutman,et al.  Serum levels of IgE‐binding factor (soluble CD23) in diseases associated with elevated IgE , 1990, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[12]  M. Dierich,et al.  Human complement factor H: An additional gene product of 43kDa isolated from human plasma shows cofactor activity for the cleavage of the third component of complement , 1989, European journal of immunology.

[13]  H. Mikola,et al.  The synthesis and use of activated N-benzyl derivatives of diethylenetriaminetetraacetic acids: alternative reagents for labeling of antibodies with metal ions. , 1989, Analytical biochemistry.

[14]  N. Ling,et al.  Soluble forms of CD21 and CD23 antigens in the serum in B cell chronic lymphocytic leukaemia. , 1989, Immunology letters.

[15]  B. Chain,et al.  Endopeptidase activities associated with the plasma membrane compartment of an antigen-presenting B cell. , 1989, Clinical and experimental immunology.

[16]  N. Cooper,et al.  CR2 ligands modulate human B cell activation. , 1988, Journal of immunology.

[17]  I Hemmilä,et al.  Lanthanides as probes for time-resolved fluorometric immunoassays. , 1988, Scandinavian journal of clinical and laboratory investigation.

[18]  John D Lambris,et al.  Expression of CR2/EBV receptors on human thymocytes detected by monoclonal antibodies , 1988, European journal of immunology.

[19]  J. Hatzfeld,et al.  Binding of C3 and C3dg to the CR2 complement receptor induces growth of an Epstein-Barr virus-positive human B cell line. , 1988, Journal of immunology.

[20]  T. Schulz,et al.  Structural and functional analysis of CR2/EBV receptor by means of monoclonal antibodies and limited tryptic digestion. , 1988, Immunology.

[21]  L. Lagneaux,et al.  Elevation of IgE-binding factors in serum of patients with B cell-derived chronic lymphocytic leukemia. , 1988, Blood.

[22]  B. Myones,et al.  Identification of a spontaneously shed fragment of B cell complement receptor type two (CR2) containing the C3d-binding site. , 1987, Complement.

[23]  S. Lemon,et al.  A SECOND SITE FOR EPSTEIN-BARR VIRUS SHEDDING: THE UTERINE CERVIX , 1986, The Lancet.

[24]  D. Bentley,et al.  Complement system proteins which interact with C3b or C4b A superfamily of structurally related proteins. , 1986, Immunology today.

[25]  L. Young,et al.  EPSTEIN-BARR VIRUS RECEPTORS ON HUMAN PHARYNGEAL EPITHELIA , 1986, The Lancet.

[26]  G. Nemerow,et al.  Binding of monoclonal antibody to the Epstein Barr virus (EBV)/CR2 receptor induces activation and differentiation of human B lymphocytes. , 1985, Journal of immunology.

[27]  J. Platt,et al.  Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro. , 1985, Blood.

[28]  G. Nemerow,et al.  Identification and characterization of the Epstein-Barr virus receptor on human B lymphocytes and its relationship to the C3d complement receptor (CR2) , 1985, Journal of virology.

[29]  F. Melchers,et al.  The action of human C3 in soluble or cross‐linked form with resting and activated murine B lymphocytes , 1985, European journal of immunology.

[30]  R. Frade,et al.  Enhancement of human B cell proliferation by an antibody to the C3d receptor, the gp 140 molecule , 1985, European journal of immunology.

[31]  P. A. Biro,et al.  Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[32]  D. Fearon,et al.  Identification of a 145,000 Mr membrane protein as the C3d receptor (CR2) of human B lymphocytes. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[33]  V. Nussenzweig,et al.  Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody , 1983, The Journal of experimental medicine.

[34]  R. DiSipio,et al.  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. , 1983, Journal of immunology.

[35]  E Soini,et al.  Time-resolved fluorometer for lanthanide chelates--a new generation of nonisotopic immunoassays. , 1983, Clinical chemistry.

[36]  P. Lobo,et al.  In vitro studies on the immune regulatory role of complement receptors (C3) present on human B lymphocytes , 1982, European journal of immunology.

[37]  J. Lambris,et al.  Isolation of lymphocyte membrane complement receptor type two (the C3d receptor) and preparation of receptor-specific antibody. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Genco,et al.  Inhibition of lymphocyte blastogenesis by C3c and C3d. , 1979, Journal of immunology.

[39]  K. Hartmann,et al.  Stimulation of murine B lymphocytes by isolated C3b , 1975, The Journal of experimental medicine.

[40]  H. Grey,et al.  Two different complement receptors on human lymphocytes. One specific for C3b and one specific for C3b inactivator-cleaved C3b. , 1973 .