Fig. 2

PD-1 signaling in B cells and T cells. a In B cells, upon PD-1 activation, SHP-2 is recruited to the C-terminal of PD-1 and dephosphorylates downstream members of the BCR pathway (e.g., SyK, Igα/β), thereby disrupting the normal BCR response as well as inhibiting PLCγ2, ERK, and PI3K signaling. This PD-1 activation consequently reduces the stability of the immunological synapse as well as B cell cycle arrest and causes disorder of Ca²⁺ mobilization. b In T cells, when PD-1 combines with PD-L1, SHP-1/2 are recruited to the C-terminal of PD-1 immediately and dephosphorylate key signal transducers, including the ZAP70, CD3δ, and PI3K pathways, thus suppressing TCR-mediated cell proliferation and cytokine production