Figure 1.

TLR7 drives the extrafollicular B-cell response and the loss of germinal centre (GC) tolerance, which is implicated in the pathogenesis of SLE. 1. Resting naive B cells enter the germinal centre pathway, which generates DN1 B cells and memory B cells, and then differentiate into antibody-secreting cells. The above processes are dependent on TLR7. 2. TLR7 drives the extrafollicular pathway, in which resting naive B cells successively become activated naive B cells, DN2 subset B cells and finally antibody-secreting cells. 3. pDC and T cells intensify TLR7 sensitivity to drive autoreactive B-cell development into antibody-secreting cells by secreting IFN-I, IFN-γ and IL-21.