BAFF promotes T cell activation through the BAFF-BAFF-R-PI3K-Akt signaling pathway

Abstract

B-cell activating factor from the tumor necrosis factor family (BAFF) has revealed its critical role in B cell proliferation and survival, as well as the pathogenesis of T-cell mediated autoimmune disease. However, the effect and molecular mechanisms of BAFF on T cell physiological function have not been fully elucidated. In this study it was seen that BAFF can promote the vitality of purified T cells, increase the proportion of CD3⁺CD4⁺, CD4⁺CD25⁺, CD4⁺CD154⁺, and CD4⁺CD69⁺ subgroups and reduce the proportion of CD4⁺CD62L⁺ subgroups. Negating BAFF activity with Atacicept (TACI-Fc) reverses vitality and activation of T cells. Furthermore, immunofluorescence detection revealed that BAFF promotes the expression of BAFF receptor (BAFF-R) and transmembrane activator and CAML interactor (TACI) in T cells. Flow cytometry displayed that BAFF/BAFF-R activates the PI3K-Akt signaling pathway while the application of PI3K inhibitor (wortmannin) illuminated that BAFF induces T cell vitality and activation through the PI3K-Akt signaling pathway. We conclude that BAFF is involved in not only the physiology of B cells, but also that of T cells. BAFF affects physiological T-cell activation through BAFF-R-mediated activation of the PI3K-Akt signaling pathway which mirrors one of the pathological mechanisms of T cell-mediated autoimmune diseases.

Keywords: B-cell activating factor from the tumor necrosis factor family (BAFF); B-cell activating factor from the tumor necrosis factor family receptor (BAFF-R); Phosphoinositide 3-kinase (PI3K); T cell activation; Transmembrane activator and CAML interactor (TACI).