Role of regulatory B cells in immune tolerance to allergens and beyond

Immune tolerance to both self-antigens and innocuous non-self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion. However, IL-35 and TGF-beta have also been associated with B cell-mediated immunosuppression. Several types of murine and human Breg cells have been described, such as mouse CD5(+)CD1d(hi)B10 cells, CD21(hi)CD23(hi)CD24 hi transitional stage 2-like B cells, and CD138(+) plasma cells and plasmablasts. Human Breg cell types include CD27(+) CD24(high) B10 cells, CD24(hi)CD38(hi) immature transitional B cells, and CD73(-)CD25(+)CD71(+) B(R)1 cells and a subset of plasma cells. Support for the in vivo existence of allergen-specific human Breg cells comes from direct detection of their increase during the course of allergen-specific immunotherapy, as well as their increased expression in nonallergic but high-dose allergen-exposed beekeepers. Human B(R)1 cells selectively upregulate IgG(4) antibodies on differentiation to plasma cells. This suggests an additional immune regulatory role because of the noninflammatory and blocking antibody function of IgG(4). Taken together, Breg cells appear to be involved in mediating allergen tolerance, but many open questions remain to be answered.