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Publication : The composite cytokine p28/cytokine-like factor 1 sustains B cell proliferation and promotes plasma cell differentiation.

First Author  Tormo AJ Year  2013
Journal  J Immunol Volume  191
Issue  4 Pages  1657-65
PubMed ID  23836062 Mgi Jnum  J:205702
Mgi Id  MGI:5546273 Doi  10.4049/jimmunol.1201595
Citation  Tormo AJ, et al. (2013) The composite cytokine p28/cytokine-like factor 1 sustains B cell proliferation and promotes plasma cell differentiation. J Immunol 191(4):1657-65
abstractText  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-27Ralpha-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.
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