Biphasic Effects on Allergen‐Specific Type 2 Memory B Cells Over 18 Months Sublingual Immunotherapy for House Dust Mite Allergy

ABSTRACT Background Type 2 memory B cells (Bmem) are the reservoir of pathogenic IgE in allergies. Allergen immunotherapy (AIT) can change the course of disease, but if it involves reprogramming of allergen‐reactive Bmem remains unknown. Here, we examine how AIT affects allergen‐specific Bmem in house dust mite (HDM) allergic patients. Methods HDM allergic patients were longitudinally evaluated over 18 months with or without sublingual HDM‐AIT. Visual analog scores, lung function tests, medication scores, serum IgE, and flowcytometric analysis of Der p 1 and Der p 2‐specific Type 2 Bmem were performed at t = 0, 4, 12, and 18 months. Results Patients on HDM‐AIT showed clinical improvement over 18 months with reduced intake of other medications and increases in specific serum IgE, IgG2, and IgG4. Allergen‐specific Bmem and the proportions of Type 2 Bmem therein became more abundant at 4 and 12 months and showed upregulation of CD29 and IgG4. At 18 months, the Type 2 Bmem proportions were reduced. Conclusion A biphasic Bmem response with early phenotypic changes followed by loss of the Type 2 state was observed during 18 months of AIT. As durable unresponsiveness takes 18 months of AIT, deletion of Type 2 Bmem is likely an important step in disease attenuation. Interventions that expedite this outcome may be beneficial in driving remission.