BANK1 controls IL-6 secretion and a Type I interferon signature via a p38 and MNK1/2- eIF4E translation initiation pathway (P4060)

Abstract

BANK1, an adaptor protein expressed in B-cells, is genetically associated with human SLE and plays a little understood role in B-cell signaling. Because BANK1 contains an N-terminal putative Toll-interleukin 1 receptor (TIR) domain, we used murine Bank1-/- splenic B cells to test if BANK1 affects signaling induced by the TLR9 agonist CpG. Following CpG stimulation BANK1 deficiency reduced p38 phosphorylation without affecting that of ERK or JNK and to reduced IL-6 secretion. Bank1-/- cells showed reduced phosphorylation of MNK1/2, confirming that BANK1 affects p38 signaling, and expression microarray analysis showed a disregulated type I interferon response. Microarray analysis and reduced phosphorylation of eIF4E indicated general repression of the eIF4F translation initiation complex in Bank1-/- cells. Together these data establish previously unrecognized roles for BANK1 in CpG-induced responses by splenic B cells. BANK1 may regulate type I IFN responses to TLR9 stimulation by influencing p38 signaling and the eIF4F complex, and thereby influence the course of viral infections or autoimmunity.