| First Author | Getahun A | Year | 2017 |
| Journal | J Exp Med | Volume | 214 |
| Issue | 4 | Pages | 931-941 |
| PubMed ID | 28341640 | Mgi Jnum | J:241860 |
| Mgi Id | MGI:5903792 | Doi | 10.1084/jem.20160972 |
| Citation | Getahun A, et al. (2017) Impaired B cell function during viral infections due to PTEN-mediated inhibition of the PI3K pathway. J Exp Med 214(4):931-941 |
| abstractText | Transient suppression of B cell function often accompanies acute viral infection. However, the molecular signaling circuitry that enforces this hyporesponsiveness is undefined. In this study, experiments identify up-regulation of the inositol phosphatase PTEN (phosphatase and tensin homolog) as primarily responsible for defects in B lymphocyte migration and antibody responses that accompany acute viral infection. B cells from mice acutely infected with gammaherpesvirus 68 are defective in BCR- and CXCR4-mediated activation of the PI3K pathway, and this, we show, is associated with increased PTEN expression. This viral infection-induced PTEN overexpression appears responsible for the suppression of antibody responses observed in infected mice because PTEN deficiency or expression of a constitutively active PI3K rescued function of B cells in infected mice. Conversely, induced overexpression of PTEN in B cells in uninfected mice led to suppression of antibody responses. Finally, we demonstrate that PTEN up-regulation is a common mechanism by which infection induces suppression of antibody responses. Collectively, these findings identify a novel role for PTEN during infection and identify regulation of the PI3K pathway, a mechanism previously shown to silence autoreactive B cells, as a key physiological target to control antibody responses. |
