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(high)CD27(+ )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(high)CD27(+) cells. Furthermore, OCS decreased IL-10 expression by CD27(+) TBs, all 3 CD24(high)CD27(+) 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.