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 hematopoietin 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, indicating that subsequent...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1997-10, Vol.94 (22), p.12041-12046
Main Authors: Devergne, O, Birkenbach, M, Kieff, E
Format: Article
Language:English
Subjects:
Animals
Antibodies
B lymphocytes
Biological Sciences
Cell culture techniques
Cell lines
Cellular immunity
COS Cells
Culture media
Dimerization
Epstein-Barr virus
Female
Genes
Glycoproteins - genetics
Glycoproteins - metabolism
Hematopoietic cell growth factors
Hematopoietic Cell Growth Factors - metabolism
Herpesvirus 4, Human
Humans
Immunity (Disease)
Interleukin-12 - genetics
Interleukin-12 - metabolism
Interleukins
Minor Histocompatibility Antigens
Pregnancy
Protein Binding
Receptors
Receptors, Cytokine
Recombinant Proteins - metabolism
Secretion
T lymphocytes
Trophoblasts
Tumor Cells, Cultured
Viruses
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Summary:The Epstein-Barr virus-induced gene 3 (EBI3) is a novel soluble hematopoietin 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, indicating that subsequent processing and secretion might be dependent on association with a second subunit. Coimmunoprecipitations from lysates and 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 EBI3 and p35 mutually facilitates their secretion. Most importantly, a large fraction of p35 in extracts of the trophoblast component of a human full-term normal placenta specifically coimmunoprecipitated with EBI3, indicating that EBI3 is in a heterodimer with p35, in vivo. Because EBI3 is expressed in EBV-transformed B lymphocytes, tonsil, spleen, and placental trophoblasts, the EBI3/p35 heterodimer is likely to be an important immunomodulator.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.94.22.12041