Abstract
BackgroundAKT2 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.MethodsIn this study, we used AKT2 knockout mice model to study the role of AKT2 in BCR signaling and B cell differentiation.ResultsAKT2 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.ConclusionsAKT2 involves in the humoral responses, and promotes the BCR signaling and actin remodeling to enhance the activation of B cells via regulating CD19 phosphorylation.E2Qk5NqwnEMPV-C1CqpUy1Video
Highlights
AKT serine/theonine kinase 2 (AKT2) is one of the key molecules that involves in the insulin-induced signaling and the development of cancer
AKT2 deficiency leads to decreased number of germinal center (GC) B cells and reduced serum levels of specific antibodies in mice To determine the effect of AKT2 on the differentiation of B cells in the periphery, we investigated the percentage and cell numbers of follicular B (FO) cells, marginal zone B (MZ) cells and germinal center (GC) B cells in the spleen from 8-week old wild-type (WT) and AKT2 KO mice
We found that AKT2 did not have any impact on the differentiation of FO and MZ B cells in mice (Fig. 1a-d), whereas non-immunized AKT2 KO mice had markedly reduced numbers and percentage of GC B cells (Fig. 1e-g)
Summary
AKT2 is one of the key molecules that involves in the insulin-induced signaling and the development of cancer. AKT2 is involved in type II diabetes and is one of the important kinases that transduce insulin-induced signals to regulate glucose and lipid metabolism [4, 5]. Patients with a loss-of-function mutation of AKT2 suffered from the autosomal dominant inheritance of severe insulin resistance and diabetes mellitus [6], and AKT2 KO mice have been reported to exhibit hyperglycemia, hyperinsulinemia and glucose intolerance [7]. AKT2 is expressed highly in numerous types of tumor cells, and there is a strong correlation between the high expression of AKT2 and the development of the malignant tumors in the liver, pancreas and colon [8,9,10]
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