B cell-intrinsic Ssu72 phosphatase is a key regulator of allergic asthma

Abstract B cell-derived immunoglobulin E (IgE) plays a crucial role in the development of allergic asthma. However, the intrinsic regulation of B cell function in this context is not fully understood. Here we investigated the role of Ssu72 phosphatase expressed in B cells during house dust mite (HDM)-induced asthma. Ssu72 expression was significantly increased in B cells stimulated with anti-CD40 and IL-4, as well as in B cells infiltrating the lungs of HDM-induced asthmatic mice. Notably, mice with B cell-specific deletion of Ssu72 exhibited considerably milder lung inflammation and lower serum levels of IgG1 and IgE compared to wild-type mice in HDM-induced asthma. In addition, the absence of Ssu72 in B cells resulted in a reduction in the number of IgG1- and IgE class-switched B cells and a decrease in soluble CD23 production, which correlated with lower expression of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) and matrix metalloproteinase 9 (MMP9). Mechanistically, our findings suggest that Ssu72 deficiency may dysregulate the AMPK–mTORC1 balance through hyperphosphorylation of AMPKα. In adoptive transfer experiments, Ssu72-deficient B cells were less effective than wild-type B cells in promoting the effector phase of HDM-induced asthma in B cell-deficient hosts following HDM sensitization. Furthermore, B cell-specific deletion of Ssu72 led to the reduced production of IL-4 and IL-13 by CD4⁺ T cells and diminished MHC class II upregulation in lymph nodes and lung B cells during HDM-induced asthma. These findings identify B cell Ssu72 as a crucial regulator of B cell activation and function in allergic asthma.