| First Author | Jellusova J | Year | 2013 |
| Journal | Cell Rep | Volume | 5 |
| Issue | 4 | Pages | 1022-35 |
| PubMed ID | 24239354 | Mgi Jnum | J:205520 |
| Mgi Id | MGI:5545698 | Doi | 10.1016/j.celrep.2013.10.022 |
| Citation | Jellusova J, et al. (2013) Context-specific BAFF-R signaling by the NF-kappaB and PI3K pathways. Cell Rep 5(4):1022-35 |
| abstractText | BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the noncanonical NF-kappaB pathway regulated by the TRAF3/NIK/IKK1 axis. We show that deletion of Ikk1 during early B cell development causes a partial impairment in B cell maturation and BAFF-dependent survival, but inactivation of Ikk1 in mature B cells does not affect survival. We further show that BAFF-R employs CD19 to promote survival via phosphatidylinositol 3-kinase (PI3K), and that coinactivation of Cd19 and Ikk1 causes a profound block in B cell maturation at the transitional stage. Consistent with a role for PI3K in BAFF-R function, inactivation of PTEN mediates a partial rescue of B cell maturation and function in Baff(-/-) animals. Elevated PI3K signaling also circumvents BAFF-dependent survival in a spontaneous B cell lymphoma model. These findings indicate that the combined activities of PI3K and IKK1 drive peripheral B cell differentiation and survival in a context-dependent manner. |
