Role of ubiquitin ligase Cbl-b in B-cell activation of dendritic cells loaded with Tα146-162 in the treatment of experimental autoimmune myasthenia gravis in mice.

OBJECTIVE: This study aimed to examine the mechanism of Tα146-162-iMDC in the pathogenic intervention of mice with experimental autoimmune myasthenia gravis (EAMG) from the perspective of B-cell activation.

MATERIALS AND METHODS: The mice were divided into three groups, model (A), intervention (B), and control (C), with the intervention of Tα146-162-iMDC. The expressions of Cbl-b mRNA, Syk, Lyn, Btk, and phospholipase C (PLC)-γ2 proteins and their phosphorylated proteins were detected.

RESULTS: The Cbl-b mRNA expression in group A was lower than that in group C (p < 0.01) while that in group B increased compared with that in group A (p < 0.05), but was lower than that in group C (p < 0.05). The expression and phosphorylation of Syk and PLC-γ2 proteins in group A increased compared with those in group C (p < 0.01) while those in group B decreased compared with those in group A (p < 0.05), but were higher than those in group C (p < 0.05). The expression and phosphorylation of Lyn protein in group A decreased compared with those in group C (p < 0.01) while those in group B increased compared with those in group A (p < 0.05), but were lower than those in group C (p < 0.05). The Btk protein expression in group A increased compared with that in group C (p < 0.01) while that in group B decreased compared with that in group A (p < 0.05), but was still higher than that in group C (p < 0.05). However, no difference in phosphorylation levels among the three groups was observed (p > 0.05).

CONCLUSIONS: Tα146-162-iMDC intervention can reduce the incidence of EAMG and may be associated with Cbl-b in the negative regulation of B-cell activation.