title: The Epstein-Barr virus-binding site on CD21 is involved in CD23 binding and interleukin-4-induced IgE and IgG4 production by human B cells.
abstract: Human CD21 has previously been described as a receptor for the C3d,g and iC3b proteins of complement, as a receptor for the gp350/220 envelope glycoprotein of the Epstein-Barr virus (EBV) and also as a receptor for inerferon-alpha (IFN-alpha). Structurally, CD21 consists of 15 to 16 short consensus repeats (SCR) of 60 to 75 amino acids followed by a transmembrane domain and an intracytoplasmic region. We reported that CD23, a low-affinity receptor for IgE (Fc epsilon R2), is a new functional ligand for CD21. We recently found that the sites of interaction of CD23 on CD21 are on SCR 5 to 8 and 1-2. The first site is a lectin-sugar type of interaction and the second site is a protein-protein interaction. We report here that amongst the other ligands for CD21 (EBV, C3d,g and IFN-alpha), only EBV is able to inhibit the binding of CD23 to CD21. Furthermore, even a peptide from gp350/220 of EBV known to bind to CD21 is able to decrease CD23 binding to CD21. Since CD23/CD21 pairing is important in the control of IgE production, we tested the effect of the EBV-derived peptide on immunoglobulin production from peripheral blood mononuclear cells and purified tonsillar B cells. Interestingly, the EBV-peptide inhibited IgE and IgG4 production induced by interleukin-4, in a dose-dependent manner. The same results were obtained using either peripheral blood mononuclear cells or purified tonsillar B cells. Another CD21 ligand, C3, did not affect binding of CD23 to CD21 nor the production of IgE and IgG4. This study indicates that blocking CD23 binding to CD21 SCR 2 on human B cells selectively modulates immunoglobulin production.
authors.affiliation: Glaxo Institute for Molecular Biology, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Henchoz-Lecoanet
authors.forename: P
authors.initials: P
authors.lastname: Jeannin
authors.forename: J P
authors.initials: JP
authors.lastname: Aubry
authors.forename: P
authors.initials: P
authors.lastname: Graber
authors.forename: C G
authors.initials: CG
authors.lastname: Bradshaw
authors.forename: S
authors.initials: S
authors.lastname: Pochon
authors.forename: J Y
authors.initials: JY
authors.lastname: Bonnefoy
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017464:Receptors, Complement 3d / Q000276:immunology / Q000378:metabolism*; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism*; D014764:Viral Proteins / Q000494:pharmacology
chemical_list: D007074:Immunoglobulin G; D007136:Immunoglobulins; D017464:Receptors, Complement 3d; D017455:Receptors, IgE; D014764:Viral Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E