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

By K. Good-Jacobson, Courtney G. Szumilas, Lieping Chen, Arlene H. Sharpe, M. Tomayko, M. Shlomchik. Nature Immunology, 2010

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Memory B and plasma cells (PCs) are generated in the germinal center (GC). Because follicular helper T cells (TFH 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 TFH 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 TFH cell and PC numbers. Thus, PD-1 regulates selection and survival in the GC, affecting the quantity and quality of long-lived PCs.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/fd3703d03b965e5d8d9fdb33f23bdc71e5992925

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Citations in the corpus

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. (2016, background): “Other immune cells may play a role in the development of irAEs, including B cells that secrete antibodies that may mediate toxicity [16, 17], granulocytes that secrete inflammatory mediators, and cytokines [16, 18].”
CD4⁺ follicular helper T cell infiltration predicts breast cancer survival. (2013, positive): “Murine studies have shown that PD-1 + Tfh cell interactions with PD-L1 + /PD-L2 + B cells are important for regulating GC activities, with a deficiency in PD-L2 resulting in reduced Tfh IL-21 production and the generation of fewer plasma cells (53).”
T follicular helper cell differentiation, function, and roles in disease (2014, background): “, 2011), and select high-affinity B cells during affinity maturation (Good-Jacobson et al., 2010; Victora et al., 2010).”
Bcl6 dependent T follicular helper cell differentiation diverges from effector cell differentiation during priming and depends on the gene Icos (2011, positive): “Tfh cells are crucial for the development of germinal centers, from which long-lived plasma cells and memory B cells are predominantly generated (Allen et al., 2007; Good-Jacobson et al., 2010).”
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. (2015, background): “Other immune cells may play a role in the development of irAEs, including B cells that secrete antibodies that may mediate toxicity [16, 17], granulocytes that secrete inflammatory mediators, and cytokines [16, 18].”