LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells

Immunity
Andreia C LinoSimon Fillatreau

Abstract

B lymphocytes can suppress immunity through interleukin (IL)-10 production in infectious, autoimmune, and malignant diseases. Here, we have identified a natural plasma cell subset that distinctively expresses the inhibitory receptor LAG-3 and mediates this function in vivo. These plasma cells also express the inhibitory receptors CD200, PD-L1, and PD-L2. They develop from various B cell subsets in a B cell receptor (BCR)-dependent manner independently of microbiota in naive mice. After challenge they upregulate IL-10 expression via a Toll-like receptor-driven mechanism within hours and without proliferating. This function is associated with a unique transcriptome and epigenome, including the lowest amount of DNA methylation at the Il10 locus compared to other B cell subsets. Their augmented accumulation in naive mutant mice with increased BCR signaling correlates with the inhibition of memory T cell formation and vaccine efficacy after challenge. These natural regulatory plasma cells may be of broad relevance for disease intervention.

Citations

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Datasets Mentioned

BETA
GSE103458
PRJEB22138
Other

Methods Mentioned

BETA
Flow cytometry
Transmission electron microscopy
Electron microscopy
Infection
PCA
ELISA
Chip
PCR
RNaseq
Assay

Software Mentioned

FACS Aria
FlowJo
MarkDuplicate
limma R
affy R package
GCRMA
pheatmap R
ChipSeek
R package edgeR
Picard

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