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

Human CD21 has previously been described as a receptor for the C3d,g a nd iC3b proteins of complement, as a receptor for the gp350/220 envelo pe glycoprotein of the Epstein-Barr virus (EBV) and also as a receptor for interferon-alpha (IFN-alpha). Structurally, CD21 consists of 15 t o 16 short consensus repeats (SCR) of 60 to 75 amino acids followed by a transmembrane domain and an intracytoplasmic region. We reported th at CD23, a low-affinity receptor for IgE (Fc epsilon R2), is a new fun ctional ligand for CD21. We recently found that the sites of interacti on of CD23 on CD21 are on SCR 5 to 8 and 1-2. The first site is a lect in-sugar type of interaction and the second site is a protein-protein interaction. We report here that amongst the other ligands for CD21 (E BV, C3d,g and IFN-alpha), only EBV is able to inhibit the binding of C D23 to CD21. Furthermore, even a peptide from gp350/220 of EBV known t o bind to CD21 is able to decrease CD23 binding to CD21. Since CD23/CD 21 pairing is important in the control of IgE production, we tested th e effect of the EBV-derived peptide on immunoglobulin production from peripheral blood mononuclear cells and purified tonsillar B cells. Int erestingly, the EBV-peptide inhibited IgE and IgG4 production induced by interleukin-4, in a dose-dependent manner. The same results were ob tained using either peripheral blood mononuclear cells or purified ton sillar B cells. Another CD21 ligand, C3, did not affect binding of CD2 3 to CD21 nor the production of IgE and IgG4. This study indicates tha t blocking CD23 binding to CD21 SCR 2 on human B cells selectively mod ulates immunoglobulin production.