The role of regulatory B cells in immune regulation and childhood allergic asthma

Abstract

Background: As the most common chronic disease in childhood, asthma displays a major public health problem worldwide with the incidence of those affected rising. As there is currently no cure for allergic asthma, it is mandatory to get a better understanding of the underlying molecular mechanism.

Main body: By producing IgE antibodies upon allergen contact, B cells play a pivotal role in allergic asthma. Besides that, IL-10-secreting B cell subsets, namely regulatory B cells (Bregs), are reported in mice and humans to play a role in allergic asthma. In humans, several Breg subsets with distinct phenotypic and functional properties are identified among B cells at different maturational and differentiation stages that exert anti-inflammatory functions by expressing several suppressor molecules. Emerging research has focused on the role of Bregs in allergic asthma as well as their role for future diagnostic and preventive strategies.

Conclusion: Knowledge about the exact function of human Bregs in allergic asthma is still very limited. This review aims to summarize the current knowledge on Bregs. We discuss different human Breg subsets, several ways of Breg induction as well as the mechanisms through which they exert immunoregulatory functions, and their role in (childhood) allergic asthma.

Keywords: Allergic asthma; B cells; Childhood asthma; Immune system; Regulatory B cells.

Fig. 1

Breg suppressor molecules and their effect on other immune cells. Bregs mainly secrete the anti-inflammatory cytokines IL-10, IL-35, and TGF-β that in turn have a suppressive function on T_H1 and T_H17 cells. In addition, the conversion of CD4⁺ T cells into Tregs is induced. The transmembrane protein PD-L1 regulates cell expansion and differentiation of T_FH cells. Also, other surface-bound molecules such as MHC-II, CD19, CD73, CD39, FasL, and TIM1 as well as AhR and GrB are described to play a role in Breg-mediated immunosuppressive effects. IL, interleukin; TGF-β, transforming growth factor β; T_H, T helper cell; Treg, regulatory T cell; PD-L1, programmed cell death ligand 1; T_FH, follicular helper T cells, MHC-II, major histocompatibility complex II; FasL, Fas ligand; TIM1, T cell immunoglobulin and mucin domain 1; AhR, aryl hydrocarbon receptor; GrB, granzyme B