| First Author | Gigoux M | Year | 2014 |
| Journal | Mol Immunol | Volume | 59 |
| Issue | 1 | Pages | 46-54 |
| PubMed ID | 24486724 | Mgi Jnum | J:209802 |
| Mgi Id | MGI:5568773 | Doi | 10.1016/j.molimm.2014.01.008 |
| Citation | Gigoux M, et al. (2014) Inducible costimulator facilitates T-dependent B cell activation by augmenting IL-4 translation. Mol Immunol 59(1):46-54 |
| abstractText | The inducible costimulator (ICOS) is highly expressed in follicular helper T (Tfh) cells, a subset of CD4 T cells that migrate into the B cell zone and facilitate germinal center reactions. Although ICOS is known to play a critical role in forming the Tfh cell population during immune responses, its contribution to the effector functions of Tfh cells remains unclear. Using activated mouse splenic CD4 T cells we demonstrate that ICOS assists TCR-mediated signal transduction by potentiating the PI3K-AKT-mTOR signaling cascade that leads to hyper-phosphorylation of p70S6K and 4E-BP1, events that are known to augment cap-dependent mRNA translation. Consequently, ICOS costimulation promotes the formation of polysomes on IL-4 mRNA in a PI3K-dependent manner. Furthermore, we show that the supply of IL-4 becomes a limiting factor for T-dependent B cell activation during in vitro co-culture when the ICOS-PI3K signaling axis is disrupted in T cells. This ICOS costimulation-dependent translational control may ensure targeted delivery of IL-4 to cognate B cells during T-B collaborations in the germinal center. |
