Cell Communication and Signaling (Apr 2020)

AKT2 deficiency impairs formation of the BCR signalosome

  • Zuochen Du,
  • Di Yang,
  • Yongjie Zhang,
  • Xingtian Xuan,
  • Han Li,
  • Leling Hu,
  • Changshun Ruan,
  • Liling Li,
  • Anwei Chen,
  • Liang Deng,
  • Yan Chen,
  • Jingwen Xie,
  • Lisa S. Westerberg,
  • Lu Huang,
  • Chaohong Liu

DOI
https://doi.org/10.1186/s12964-020-00534-9
Journal volume & issue
Vol. 18, no. 1
pp. 1 – 11

Abstract

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Abstract Background AKT2 is one of the key molecules that involves in the insulin-induced signaling and the development of cancer. In B cells, the function of AKT2 is unclear. Methods In this study, we used AKT2 knockout mice model to study the role of AKT2 in BCR signaling and B cell differentiation. Results AKT2 promotes the early activation of B cells by enhancing the BCR signaling and actin remodeling. B cells from AKT2 KO mice exhibited defective spreading and BCR clustering upon stimulation in vitro. Disruption of Btk-mediated signaling caused the impaired differentiation of germinal center B cells, and the serum levels of both sepecific IgM and IgG were decreased in the immunized AKT2 KO mice. In addition, the actin remodeling was affected due to the decreased level of the activation of WASP, the actin polymerization regulator, in AKT2 KO mice as well. As a crucial regulator of both BCR signaling and actin remodeling during early activation of B cells, the phosphorylation of CD19 was decreased in the AKT2 absent B cells, while the transcription level was normal. Conclusions AKT2 involves in the humoral responses, and promotes the BCR signaling and actin remodeling to enhance the activation of B cells via regulating CD19 phosphorylation. Video Abstract