A NOVEL INTERLEUKIN-12 P40-RELATED PROTEIN-INDUCED BY LATENT EPSTEIN-BARR-VIRUS INFECTION IN B-LYMPHOCYTES

We have isolated a cDNA encoding a novel hematopoietin receptor family member related to the p40 subunit of interleukin-12 and to the ciliar y neurotrophic factor receptor, whose expression is induced in B lymph ocytes by Epstein-Barr virus (EBV) infection, This gene, which we have designated EBV-induced gene 3 (EB13), encodes a 34-kDa glycoprotein w hich lacks a membrane-anchoring motif and is secreted, Despite the abs ence of a membrane-anchoring motif and of cysteines likely to mediate covalent linkage to an integral membrane protein, EBI3 is also present on the plasma membrane of EBV-transformed B lymphocytes and of transf ected cells. Most newly synthesized EBI3 is retained in the endoplasmi c reticulum in an endoglycosidase H-sensitive form associated with the molecular chaperone calnexin and with a novel 60-kDa protein, EBI3 is expressed in vivo by scattered cells in interfollicular zones of tons il tissue, by cells associated with sinusoids in perifollicular areas of spleen tissue, and at very high levels by placental syncytiotrophob lasts. EB13 expression in vitro is induced in EBV-negative cell lines by expression of the EBV latent infection membrane protein-1 and in pe ripheral blood mononuclear cells by pokeweed mitogen stimulation, EB13 maps to chromosome 19p313.2/3, near genes encoding the erythropoietin receptor and the cytokine receptor-associated kinase, Tyk2, EBI3 synt hesis by trophoblasts and by EBV-transformed cells and similarities to interleukin-12 p40 are compatible with a role for EBI3 in regulating cell-mediated immune responses.