PhD student Sungkyunkwan University, United States
Disclosure(s):
NAIYU WANG, PhD: No financial relationships to disclose
Introduction/Rationale: B cell–derived immunoglobulin E (IgE) and B cell antigen presentation play a central role in allergic asthma, but the B cell signaling pathways responsible for allergic asthma remain incompletely understood. Although phosphatases regulate key processes in protein activity via dephosphorylation, their roles in B cells are largely under explored.
Methods: Here, we investigated the role of a dual protein phosphatase (DPP) in B cells during house dust mite (HDM)-induced asthma. B cell–specific DDP knockout mice were generated and used to establish HDM-induced asthma. Class switch recombination (CSR) to IgE and IgG1, and CD23 shedding ability in B cells were assessed in vitro, followed by adoptive transfer experiments using DDP-deficient B cells into μMT-/- mice.
Results: The expression of DPP was strongly induced in B cells stimulated with anti-CD40 or IL-4, as well as in B cells infiltrating HDM–induced asthmatic lungs. Mice with B cell–specific deletion of DPP developed significantly milder HDM-induced asthma compared with wild-type controls. There was also a loss of DPP impaired class switching to IgE and IgG1, and reduced CD23 shedding due to decreased ADAM10 expression in B cells. In adoptive transfer experiments, DPP-deficient B cells were less effective than wild-type B cells in promoting the late phase of HDM-induced asthma in B cell–deficient hosts after HDM sensitization. Moreover, B cell–specific DPP deficiency reduced IL-4 and IL-13 production by CD4⁺ T cells and diminished MHC class II upregulation in lymph nodes and lung B cells during HDM-induced asthma.
Conclusion: Collectively, these findings identify DPP in B cells as a regulator of IgE class switching and asthmatic TH2 inflammation.
