Soluble CD23 Monomers Inhibit and Oligomers Stimulate IGE Synthesis in Human B Cells*

The low affinity IgE receptor, CD23, is implicated in IgE regulation and the pathogenesis of allergic disease. CD23 is a type II integral membrane protein, comprising a lectin “head,” N-terminal “stalk,” and C-terminal “tail” in the extracellular sequence. Endogenous proteases cleave CD23 in the stalk and the tail to release soluble fragments that either stimulate or inhibit IgE synthesis in human B cells. The molecular basis of these paradoxical activities is not understood. We have characterized three fragments of CD23, monomeric derCD23, monomeric exCD23, and oligomeric lzCD23. We show that the monomers inhibit and the oligomer stimulates IgE synthesis in human B cells after heavy chain switching to IgE. CD23 fragments could be targets for therapeutic intervention in allergic disease.

[1]  P. Lipsky,et al.  The Low Affinity IgE Receptor (CD23) Is Cleaved by the Metalloproteinase ADAM10* , 2007, Journal of Biological Chemistry.

[2]  S. Umland,et al.  ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23 , 2006, Nature Immunology.

[3]  M. Keating,et al.  Monoclonal antibodies in chronic lymphocytic leukemia , 2006, Expert review of anticancer therapy.

[4]  Rebecca L. Beavil,et al.  The structure of human CD23 and its interactions with IgE and CD21 , 2005, The Journal of experimental medicine.

[5]  J. Inman,et al.  Role of Complement-Binding CD21/CD19/CD81 in Enhancing Human B Cell Protection from Fas-Mediated Apoptosis 1 , 2003, The Journal of Immunology.

[6]  S. Durham,et al.  Activity of human monocytes in IgE antibody‐dependent surveillance and killing of ovarian tumor cells , 2003, European journal of immunology.

[7]  David Fear,et al.  The biology of IGE and the basis of allergic disease. , 2001, Annual review of immunology.

[8]  Andrew Beavil,et al.  Necessity of the stalk region for immunoglobulin E interaction with CD23 , 2002, Immunology.

[9]  M. Reff,et al.  Anti-CD23 monoclonal antibody inhibits germline Cε transcription in B cells , 2002 .

[10]  S. Pierce.  Lipid rafts and B-cell activation , 2002, Nature Reviews Immunology.

[11]  M. Malaise,et al.  Increased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA) , 2000, Clinical and experimental immunology.

[12]  P. Brams,et al.  In vitro IgE inhibition in B cells by anti-CD23 monoclonal antibodies is functionally dependent on the immunoglobulin Fc domain. , 2000, International journal of immunopharmacology.

[13]  P. Emery,et al.  Increased expression of CD23 in rheumatoid synovitis. , 2000, Scandinavian journal of rheumatology.

[14]  E. C. Snow,et al.  Cutting edge: recruitment of the CD19/CD21 coreceptor to B cell antigen receptor is required for antigen-mediated expression of Bcl-2 by resting and cycling hen egg lysozyme transgenic B cells. , 1999, Journal of immunology.

[15]  F. Lindberg,et al.  The Vitronectin Receptor and its Associated CD47 Molecule Mediates Proinflammatory Cytokine Synthesis in Human Monocytes by Interaction with Soluble CD23 , 1999, The Journal of cell biology.

[16]  Y. Nakai,et al.  Decrease of Serum Levels of Soluble CD23 during Immunotherapy in Patients with Perennial Allergic Rhinitis , 1999, The Annals of otology, rhinology, and laryngology.

[17]  D. Conrad,et al.  Production of a Chimeric Form of CD23 That Is Oligomeric and Blocks IgE Binding to the FcεRI , 1998, The Journal of Immunology.

[18]  A. Gagro,et al.  Expression of CD23 antigen and its ligands in children with intrinsic and extrinsic asthma , 1997, Allergy.

[19]  D. Conrad,et al.  Mouse CD23 regulates monocyte activation through an interaction with the adhesion molecule CD11b/CD18 , 1997, European journal of immunology.

[20]  L. Nitschke,et al.  Effect of transmembrane and cytoplasmic domains of IgE on the IgE response. , 1997, Science.

[21]  R. Owens,et al.  Interaction of the Low-Affinity Receptor CD23/FcεRII Lectin Domain with the Fcε3−4 Fragment of Human Immunoglobulin E† , 1997 .

[22]  B. Čvoriščec,et al.  Decrease in CD23+ B lymphocytes and clinical outcome in asthmatic patients receiving specific rush immunotherapy. , 1996, International archives of allergy and immunology.

[23]  Rajko Reljic,et al.  The interaction of CD23 and CR2 and its functional consequences. , 1996 .

[24]  H. Sewell,et al.  Der p I, a major allergen of the house dust mite, proteolytically cleaves the low‐affinity receptor for human IgE (CD23) , 1995, European journal of immunology.

[25]  R. Ghirlando,et al.  Stoichiometry and thermodynamics of the interaction between the Fc fragment of human IgG1 and its low-affinity receptor Fc gamma RIII. , 1995, Biochemistry.

[26]  J. Bonnefoy,et al.  CD23/Fc epsilon RII and its soluble fragments can form oligomers on the cell surface and in solution. , 1995, Immunology.

[27]  R. Owens,et al.  Secretion of recombinant human IgE-Fc by mammalian cells and biological activity of glycosylation site mutants. , 1995, Protein engineering.

[28]  D. Fearon,et al.  The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. , 1995, Annual review of immunology.

[29]  Tom Alber,et al.  Crystal structure of an isoleucine-zipper trimer , 1994, Nature.

[30]  G. Köhler,et al.  Negative feedback regulation of IgE synthesis by murine CD23 , 1994, Nature.

[31]  V. Holers,et al.  CD23 interacts with a new functional extracytoplasmic domain involving N-linked oligosaccharides on CD21. , 1994, Journal of immunology.

[32]  D. Conrad,et al.  The oligomeric nature of the murine Fc epsilon RII/CD23. Implications for function. , 1993, Journal of immunology.

[33]  E. Hay,et al.  Soluble CD23 levels are elevated in the serum of patients with primary Sjögren's syndrome and systemic lupus erythematosus , 1992, Clinical and experimental immunology.

[34]  J. Bonnefoy,et al.  Demonstration of a second ligand for the low affinity receptor for immunoglobulin E (CD23) using recombinant CD23 reconstituted into fluorescent liposomes , 1992, The Journal of experimental medicine.

[35]  S. Fournier,et al.  The Low‐Affinity Receptor for IgE , 1992, Immunological reviews.

[36]  A. Beavil,et al.  Alpha-helical coiled-coil stalks in the low-affinity receptor for IgE (Fc epsilon RII/CD23) and related C-type lectins. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  M. Neuberger,et al.  The B-cell antigen receptor of the five immunoglobulin classes , 1991, Nature.

[38]  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.

[39]  E. Rieber,et al.  IgE‐dependent antigen focusing by human B lymphocytes is mediated by the low‐affinity receptor for IgE , 1990, European journal of immunology.

[40]  G. Delespesse,et al.  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. , 1989, Molecular immunology.

[41]  M. Kehry,et al.  Low-affinity IgE receptor (CD23) function on mouse B cells: role in IgE-dependent antigen focusing. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[42]  J. Cairns,et al.  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. , 1989, Immunology.

[43]  H. Kikutani,et al.  Two species of human Fcε receptor II ( FcεRII CD23 ): Tissue-specific and IL-4-specific regulation of gene expression , 1988, Cell.

[44]  G. Delespesse,et al.  Cloning and expression of the cDNA coding for a human lymphocyte IgE receptor. , 1987, The EMBO journal.

[45]  T. Hirano,et al.  Molecular structure of human lymphocyte receptor for immunoglobulin E , 1986, Cell.

[46]  A. Sehon,et al.  In vitro synthesis of IgE by human lymphocytes. IV. Suppression of the spontaneous IgE synthesis by IgE-binding factors secreted by tunicamycin-treated RPMI 8866 cells. , 1984, Immunology.

[47]  A. Sehon,et al.  In vitro synthesis of IgE by human lymphocytes. III. IgE-potentiating activity of culture supernatants from Epstein-Barr virus (EBV) transformed B cells. , 1984, Immunology.

[48]  A. Sehon,et al.  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. , 1984, Immunology.

[49]  H. Spiegelberg,et al.  Structure and function of Fc receptors for IgE on lymphocytes, monocytes, and macrophages. , 1984, Advances in immunology.