Persistent Off‐Season Dysregulation of Memory B Cell Subsets in Allergic Rhinitis

ABSTRACT Introduction Allergic rhinitis (AR) is a common allergic airway disease. Although B cells play essential roles in AR pathogenesis, their subset distribution outside the allergen exposure period remains poorly characterized. Objective To profile peripheral blood B cell subsets in AR patients during the pollen‐free season and compare them with healthy controls (HC), aiming to identify persistent immunological alterations and potential biomarkers. Methods Peripheral blood mononuclear cells (PBMCs) were collected from a total of 28 participants, 14 patients with allergic rhinitis (AR) and 14 healthy controls (HC) during the off‐season. B cell subsets were identified using flow cytometry based on IgD and CD27 expression, classifying cells as naïve (IgD + CD27 − ), unswitched memory (IgD + CD27 + ), switched/conventional memory (IgD − CD27 + ), and unconventional memory B cells (IgD − CD27 − ). CD38 and CD24 were utilized to further distinguish transitional, naïve, memory, and plasma cell phenotypes. Immunoglobulin isotypes (IgG1‐4, IgA1 + /IgA2 + ) were assessed specifically within conventional memory B cells, while CD86 expression was evaluated on IgM + memory‐like and naïve B cells. Additionally, kappa ( κ ) and lambda ( λ ) light chain usage was analyzed to assess light chain distribution. Results AR patients displayed lower frequencies of IgG1 + , IgG2 + , and IgA1 + /IgA2 + memory B cells, along with elevated frequencies of IgG4 + and κ + B cells. Additionally, CD86 + IgM + memory‐like B cells were significantly reduced in AR, suggesting altered activation dynamics. No significant differences were observed in CD24/CD38 profiling. Conclusion Even outside allergen exposure, AR patients exhibit systemic B cell dysregulation, characterized by skewed class switching, altered subset distribution, and reduced activation markers expression. These findings underscore persistent immune imbalance in AR, identify potential off‐season biomarkers of allergic inflammation.