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

Kim L Good-Jacobson, Courtney G Szumilas, Lieping Chen, Arlene H Sharpe, Mary M Tomayko, Mark J Shlomchik

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412 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)535 - 542
Number of pages8
JournalNature Immunology
Volume11
Issue number6
DOIs
Publication statusPublished - 2010
Externally publishedYes

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