title: The composite cytokine p28/cytokine-like factor 1 sustains B cell proliferation and promotes plasma cell differentiation.
abstract: IL-27 is an APC-derived IL-6/IL-12 family composite cytokine with multiple functions such as regulation of Th1, Th17, and regulatory T cell differentiation, B cell proliferation, and Ig class switching. The IL-27 complex is formed by the association of the cytokine p28 with the soluble cytokine receptor EBV-induced gene 3 (EBI3). The IL-27 cytokine and soluble receptor subunits p28 and EBI3 can be secreted independently. The p28 subunit has been shown to have IL-27-independent biological activities. We previously demonstrated that p28 can form an alternative composite cytokine with the EBI3 homolog cytokine-like factor 1 (CLF; CRLF1). p28/CLF modulates NK cell activity and CD4 T cell cytokine production in vitro. In this study we used IL-6-dependent plasmacytoma cell line B9 and CD4 T cells from IL-27Rα-deficient mice to demonstrate that p28/CLF activates IL-27-unresponsive cells, indicating that p28/CLF and IL-27 signal through different receptors. The observation that p28/CLF, unlike IL-27, sustains B9 plasmacytoma cell proliferation prompted us to investigate the effects of p28/CLF on mouse B cells. We observed that p28/CLF induces IgM, IgG2c, and IgG1 production and plasma cell differentiation. p28/CLF therefore has the potential to contribute to B and plasma cell function, differentiation, and proliferation in normal and pathological conditions such as Castelman's disease and multiple myeloma.
authors.affiliation: Département de Pharmacologie, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
authors.forename: Aurélie Jeanne
authors.initials: AJ
authors.lastname: Tormo
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Meliani
authors.forename: Linda Ann
authors.initials: LA
authors.lastname: Beaupré
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
authors.forename: Greg
authors.initials: G
authors.lastname: Elson
authors.forename: Sandrine
authors.initials: S
authors.lastname: Crabé
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gauchat
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002455:Cell Division; D002460:Cell Line; D005260:Female; D007136:Immunoglobulins / Q000096:biosynthesis; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D053612:Janus Kinases / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D038041:Lymphopoiesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology; D011499:Protein Processing, Post-Translational; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins / Q000276:immunology; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology; D014162:Transfection
chemical_list: C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007136:Immunoglobulins; D007378:Interleukins; D008070:Lipopolysaccharides; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D050791:STAT Transcription Factors; D053612:Janus Kinases