title: 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.
authors.affiliation: Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Good-Jacobson
authors.forename: Courtney G
authors.initials: CG
authors.lastname: Szumilas
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Arlene H
authors.initials: AH
authors.lastname: Sharpe
authors.forename: Mary M
authors.initials: MM
authors.lastname: Tomayko
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Shlomchik
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D002470:Cell Survival; D018858:Germinal Center / Q000166:cytology*; D051379:Mice; D018345:Mice, Knockout; D010950:Plasma Cells / Q000166:cytology*; D061026:Programmed Cell Death 1 Receptor
chemical_list: D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor
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