Figure 3.

Innate signaling pathways involved in the activation of autoreactive B cells. Autoreactive B cells bind DNA/RNA-containing complexes from dying cells or immune complexes (ICs), consisting of IgG bound to nuclear antigens and become activated though dual engagement of their surface B-cell receptor (BCR) and nucleic-acid sensing Toll-like receptors TLR7 and TLR9. Upon binding, the BCR internalizes and delivers DNA/RNA-containing antigens to the endosomal/lysosomal compartment. TLR7 and TLR9 traffic from the endoplasmic reticulum to endosomal/lysosomal compartments using UNC93B1 transporter. BCR and TLR signals collaborate in promoting B-cell survival, activation and proliferation. Type I interferon (IFN) (produced mostly by activated plasmacytoid dendritic cells (pDCs)) primes autoreactive B cells by promoting the expression of TLRs and synergizing with the BCR signals.