PT  - JOURNAL ARTICLE
AU  - Yukai Jing
AU  - Danqing Kang
AU  - Lu Yang
AU  - Panpan Jiang
AU  - Na Li
AU  - Jiali Cheng
AU  - Jingwen Li
AU  - Heather Miller
AU  - Boxu Ren
AU  - Quan Gong
AU  - Wei Yin
AU  - Zheng Liu
AU  - Pieta Mattila
AU  - Bing Yu
AU  - Chaohong Liu
TI  - MITA couples with PI3K to regulate actin reorganization during BCR activation
AID  - 10.1101/346445
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 346445
4099  - http://biorxiv.org/content/early/2018/06/15/346445.short
4100  - http://biorxiv.org/content/early/2018/06/15/346445.full
AB  - As an adaptor protein, MITA has been extensively studied in innate immunity. However, its role in adaptive immunity as well as its underlying mechanism are not completely understood. We used MITA KO mice to study the effect of MITA deficiency on B cell development and differentiation, BCR signaling during BCR activation and humoral immune response. We found that MITA deficiency promotes the differentiation of marginal zone B cells, which is linked to the lupus-like autoimmune disease that develops in MITA KO mice. MITA is involved in BCR activation and negatively regulates the activation of CD19 and Btk and positively regulates the activation of SHIP. Interestingly, we found that the activation of WASP and accumulation of F-actin is enhanced in MITA KO B cells upon stimulation. Mechanistically, we found that MITA uses PI3K mediated by the CD19-Btk axis as a central hub to control the actin remodeling that, in turn, offers feedback to BCR signaling. Overall, our study has provided a new mechanism on how MITA regulates BCR signaling via feedback from actin reorganization, which may contribute to the effects of MITA on the humoral immune response.