STING couples with PI3K to regulate actin reorganization during BCR activation.

Abstract

The adaptor protein, STING (stimulator of interferon genes), has been rarely studied in adaptive immunity. We used <i>Sting</i> KO mice and a patient's mutated <i>STING</i> cells to study the effect of STING deficiency on B cell development, differentiation, and BCR signaling. We found that STING deficiency promotes the differentiation of marginal zone B cells. STING is involved in BCR activation and negatively regulates the activation of CD19 and Btk but positively regulates the activation of SHIP. The activation of WASP and accumulation of F-actin were enhanced in <i>Sting</i> KO B cells upon BCR stimulation. Mechanistically, STING uses PI3K mediated by the CD19-Btk axis as a central hub for controlling the actin remodeling that, in turn, offers feedback to BCR signaling. Overall, our study provides a mechanism of how STING regulates BCR signaling via feedback from actin reorganization, which contributes to positive regulation of STING on the humoral immune response.