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.