Phenotypic and functional alterations of regulatory B cell subsets in adult allergic asthma patients

Background: IL-10-producing regulatory B cells (Bregs) are widely ascribed immune regulatory functions. However, Breg subsets in human asthma have not been fully investigated. Objective: We studied Breg subsets in adult allergic asthma patients by assessing two major parameters, frequency and IL-10 expression. We then investigated factors that affect these two parameters in patients. Methods: Peripheral blood mononuclear cells (PBMCs) of adult allergic asthma patients (N = 26) and non-asthmatic controls (N = 28) were used to assess the frequency of five subsets of transitional B cells (TBs), three subsets of CD24^highCD27⁺B cells and B1 cells. In addition to clinical data, IL-10 expression by individual Breg subsets was assessed by flow cytometry. Results: Asthma patients had decreases of CD5⁺ and CD1d⁺CD5⁺, but an increase of CD27⁺ TBs which was significant in patients with moderate asthma (60 < FEV1 < 80). Regardless of asthma severity, there was no significant alteration in the frequencies of 6 other Breg subsets tested. However, we found that oral corticosteroid (OCS) significantly affected the frequency of Bregs in Breg subset-specific manners. OCS decreased CD5⁺ and CD1d⁺CD5⁺ TBs, but increased CD27⁺ TBs and CD10⁺CD24^highCD27⁺ cells. Furthermore, OCS decreased IL-10 expression by CD27⁺ TBs, all 3 CD24^highCD27⁺ B cell subsets (CD5⁺, CD10⁺ and CD1d⁺) and B1 cells. OCS-mediated inhibition of IL-10 expression was not observed in the other Breg subsets tested. Conclusion & Clinical Relevance: Alterations in the frequency of Bregs and their ability to express IL-10 are Breg subset-specific. OCS treatment significantly affects the frequency as well as their ability to express IL-10 in Breg subset-specific manners.