Immune-tolerance impairment function of Breg cells participates in the mechanism of SLE
Breg cells participate in regulating immune responses and building the immune-tolerance milieu in autoimmune diseases and infections73-75. Breg cells suppress immune responses by decreasing the total immunoglobulin G (IgG) level, thus inhibiting the generation of plasma cells and reducing the production of antibodies in plasma cells 76-78. Some studies have proposed that IL-10+ Breg cells in SLE patients and SLE murine models have expansion defects; therefore, the frequency of Breg cells in B cells significantly decreases after in vitro stimulation, thus impairing immunosuppressive function 22, 79, 80. Moreover, it has recently been reported that plasmacytoid dendritic cells (pDCs) and Breg cells build an auto-regulatory feedback mechanism. However, the regulatory feedback mechanism is compromised in SLE. PDCs induce fewer IL-10+ Breg cells and conversely promote more differentiation of plasma cells from activated B cells, via IFN-α secretion 22. This indicates that when compromised, the regulatory functions of Breg cells break the balance between immune response and immune-tolerance (Figure 3). Previous research 22 has also indicated that the defective expansion of regulatory B cells is induced by the altered STAT3 activation of B cells in SLE. Thus, they play an important role in the mechanism of SLE.