PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells.

Memory B and plasma cells (PCs) are generated in the germinal center (GC). Because follicular helper T cells (T_FH cells) have high expression of the immunoinhibitory receptor PD-1, we investigated the role of PD-1 signaling in the humoral response. We found that the PD-1 ligands PD-L1 and PD-L2 were upregulated on GC B cells. Mice deficient in PD-L2 (Pdcd1lg2^−/−), PD-L1 and PD-L2 (Cd274^−/−Pdcd1lg2^−/−) or PD-1 (Pdcd1^−/−) had fewer long-lived PCs. The mechanism involved more GC cell death and less T_FH cell cytokine production in the absence of PD-1; the effect was selective, as remaining PCs had greater affinity for antigen. PD-1 expression on T cells and PD-L2 expression on B cells controlled T_FH cell and PC numbers. Thus, PD-1 regulates selection and survival in the GC, affecting the quantity and quality of long-lived PCs. [ABSTRACT FROM AUTHOR]