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

ABSTRACT: 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.

SUBMITTER: Good-Jacobson KL

PROVIDER: S-EPMC2874069 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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

Good-Jacobson Kim L KL Szumilas Courtney G CG Chen Lieping L Sharpe Arlene H AH Tomayko Mary M MM Shlomchik Mark J MJ

Nature immunology 20100509 6

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 deat ...[more]

PMID: 20453843

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