EPSTEIN-BARR VIRUS-INDUCED GENE-3 AND THE P35 SUBUNIT OF INTERLEUKIN-12 FORM A NOVEL HETERODIMERIC HEMATOPOIETIN

The Epstein-Barr virus-induced gene 3 (EBI3) is a novel soluble hemato poietin component related to the p40 subunit of interleukin 12 (IL-12) , When EBI3 was expressed in cells, it accumulated in the endoplasmic reticulum and associated with the molecular chaperone calnexin, indica ting that subsequent processing and secretion might be dependent on as sociation with a second subunit, Coimmunoprecipitations from lysates a nd culture media of cells transfected with expression vectors for EBI3 and/or the p35 subunit of IL-12 now reveal a specific association of EBI3 with p35, Coexpression of EBB and p35 mutually facilitates their secretion, Most importantly, a large fraction of p35 in extracts of th e trophoblast component of a human full-term normal placenta specifica lly coimmunoprecipitated with EBIS, indicating that EBI3 is in a heter odimer with p35, in vivo. Because EBI3 is expressed in EBV-transformed B lymphocytes, tonsil, spleen, and placental trophoblasts, the EBI3/p 35 heterodimer is likely to be an important immunomodulator.