Figure 2. Biological action of PD-1 blockade on mB_Act cells and antibody production during SIV infection.

(A) As shown by Titanji and colleagues, PD-1 on mB_Act of rapid progressors leads to apoptosis of these cells (3). The signal to undergo PD-1–mediated apoptosis can be provided in an autocrine fashion from PD-1 ligands present on B cells, or from PD-1 ligands on Th cells. In this context, it is likely that PD-1 present on Th cells does not receive signaling from PD-1 ligands present on B cells, since they are engaged in autocrine binding to PD-1 on B cells. (B) One possible interpretation of the data presented by Titanji et al. (3) is that upon PD-1 blockade, the autocrine binding of PD-1 to PD-1 ligands is inhibited, thus preventing apoptosis of B cells. Thus, blocking PD-1 on B cells can improve the possibility for these cells to produce specific antibodies to SIV and other microbial antigens, by channeling T cell help toward B cells in GCs.