PD-1
Overview
PD-1 (Programmed Death-1; encoded by PDCD1) is an inhibitory immune checkpoint receptor expressed on activated T and B cells. In B cell biology, PD-1 expression is upregulated on extrafollicular effector populations (DN2 and activated naive B cells) in SLE, with unique chromatin accessibility patterns at the PDCD1 locus distinguishing DN2 from isotype-switched memory B cells.
Key Points from Literature
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PD-1 protein highest on DN2 cells by flow cytometry: In SLE patients (n=4), PD-1⁺ cells were highest in DN2 (~60%) followed by aN (~20%), SM (~15%), and rN (~10%). PD-1 expression distinguished DN2 from switched memory at the protein level (see Scharer2019 - Epigenetic Programming in SLE B Cells, flow cytometry, n=4 SLE).
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PDCD1 mRNA upregulated in SLE B cells: PDCD1 was a significant DEG in SLE vs. HC, with expression peaking in DN2 cells. Expression was also already upregulated in resting naive B cells from SLE patients (see Scharer2019 - Epigenetic Programming in SLE B Cells, RNA-seq).
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PDCD1 chromatin uniquely accessible in DN2: ATAC-seq showed the PDCD1 promoter and cis-regulatory elements with highly accessible chromatin in DN2 B cells compared with isotype-switched memory cells. These DARs were boxed in genome plots as DN2-specific accessible regions (see Scharer2019 - Epigenetic Programming in SLE B Cells).
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PDCD1 demethylated and accessible in SLE resting naive B cells: The PDCD1 locus was among the genes showing correlated demethylation and increased accessibility in SLE resting naive B cells — part of the SLE disease signature already established at the earliest differentiation stage (see Scharer2019 - Epigenetic Programming in SLE B Cells).
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Suggests BCR engagement in resting naive cells: PDCD1 expression (along with AICDA) is induced by BCR signalling, and its upregulation in SLE resting naive B cells suggests these cells have received antigenic stimulation (see Scharer2019 - Epigenetic Programming in SLE B Cells).
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PD-1 is the defining marker of Tph cells in dengue: CXCR5⁻PD-1⁺ CD4⁺ T cells (Peripheral Helper T Cell) constitute ~75% of activated CD4⁺ T cells in acute dengue and are the dominant source of B cell help. PD-1 expression here marks T cell activation/exhaustion rather than B cell biology, but the convergence of PD-1 expression on both the T cell (Tph) and B cell (DN2) arms of the EF pathway is notable — PD-1⁺ Tph provide IL-21 to PD-1⁺ DN2 cells (see Ansari2025 - Peripheral T Helper Subset Drives B Cell Response in Dengue, n=170 acute dengue).
Contradictions & Debates
None documented in current wiki sources.
Related Pages
DN2 B Cell, Activated Naive B Cell, Double-Negative B Cell, Conventional Flow Cytometry, Peripheral Helper T Cell, CXCR5