Context-Specific BAFF-R Signaling by the NF-κB and PI3K Pathways

Julia Jellusova, Ana V. Miletic, Matthew H. Cato, Wai Wai Lin, Yinling Hu, Gail A. Bishop, Mark J. Shlomchik, Robert C. Rickert

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the noncanonical NF-κB 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

Original languageEnglish
Pages (from-to)1022-1035
Number of pages14
JournalCell Reports
Volume5
Issue number4
DOIs
StatePublished - 27 Nov 2013
Externally publishedYes

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