SREBP signaling critically regulates the development and function of lung resident memory B cells in allergy 4073

Description Lung resident memory B cells (BRM) are well-recognized for supporting local immunity in models of viral infection, but their role in allergic conditions is poorly understood. To investigate this, we utilized a murine model of house dust mite-driven allergic airway disease. Our studies demonstrate that repeated allergen exposure induces a population of antigen-specific BRM in the lungs, which support the local production of plasma cells and IgG1 and IgE antibodies during memory recall responses to allergen. To further explore the metabolic requirements for the generation and function of allergy-associated BRM, we focused on the SCAP-SREBP signaling pathway, which regulates sterol homeostasis during B cell responses. Our findings reveal that B cell SREBP signaling is critical for the establishment of allergic lung BRM. To determine whether this pathway is also necessary for BRM functionality after establishment, we used a tamoxifen-driven Cre system for inducible deletion of SCAP in B cells at memory timepoints. We discovered that SREBP signaling is essential for efficient reactivation of BRM during memory recall responses. These findings highlight the role of lung BRM in allergic airway disease and identify SREBP-mediated sterol metabolism as a key factor contributing to BRM generation and function. These studies suggest that targeting BRM sterol metabolism could represent a promising therapeutic strategy for treating antibody-mediated allergic disorders.