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

Immunology. 1996 May;88(1):35-9. doi: 10.1046/j.1365-2567.1996.d01-651.x.


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.

MeSH terms

  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Binding Sites
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Herpesvirus 4, Human / immunology
  • Herpesvirus 4, Human / metabolism*
  • Humans
  • Immunoglobulin E / biosynthesis
  • Immunoglobulin G / biosynthesis
  • Immunoglobulins / biosynthesis*
  • Interleukin-4 / metabolism
  • Protein Binding / drug effects
  • Receptors, Complement 3d / immunology
  • Receptors, Complement 3d / metabolism*
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism*
  • Viral Proteins / pharmacology


  • Immunoglobulin G
  • Immunoglobulins
  • Receptors, Complement 3d
  • Receptors, IgE
  • Viral Proteins
  • Interleukin-4
  • Immunoglobulin E