BANK1, an adaptor protein expressed in B-cells, plays a little understood role in B-cell signaling. Because BANK1 contains an N-terminal putative Toll-interleukin 1 receptor (TIR) domain, we used mouse 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 reduced IL-6 secretion. Bank1−/− B cells showed reduced phosphorylation of MNK1/2 and eIF4E, suggesting an effect on translation initiation, while Bank1−/− had no effect on IL6 mRNA stability, thus suggesting that BANK1 has no effect on MK2 signaling. IL-6 secretion observed when CpG stimulation was combined with anti-CD40, was reduced in the absence of BANK1. While in the presence of anti-CD40 stimulation CpG induced a stronger phosphorylation of AKT, mTOR and 4E-BP1, Bank1−/− had no effect on phosphorylation of mTOR and 4E-BP1, and weakly on AKT, implying that BANK1 does not affect the release of eIF4E by phospho-4E-BP1. Together these data establish a previously unrecognized role for BANK1 in CpG-induced responses by splenic B cells on p38 signaling and control of translation initiation of IL-6 via MNK1/2 and eIF4E.

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.