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Single cell transcriptomic profiling of human CD19+ B cells enriched for CD5+ Innate-like B cells

ABSTRACT: Aryl hydrocarbon receptor is a ligand-activated transcription factor whose activation can regulate B cell-mediated immune responses. Given the diverse nature of human B cell subsets, scRNA-seq transcriptomic profiling was used to ascertain the heterogeneity of AHR expression in discrete B cell subpopulations. We identified a unique cell cluster enriched in expression of AHR and CD9. Further, these cells were diminished in their expression of canonical B cell-associated genes and enriched with a myeloid cell-specified gene signature. These results were confirmed in vitro as CD14 expressing B cells were readily detectable in human donor PBMC and expressed significantly more AHR protein. Following activation in vitro, CD9+ B cells secreted IgM, IL-10, TGFβ1, and several myeloid-associated pro-inflammatory mediators, specifically CXCL8. These results demonstrate CD14 expression by B cells is readily detectable in healthy human donors and their release of CXCL8 could implicate these cells in inflammatory diseases and autoimmunity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221199 | GEO | 2024/12/04

REPOSITORIES: GEO

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Project description:Identification of MEK-ERK or p38MAPK dependent genes in human monocyte derived dendritic cells. Dendritic cells (DC) promote tolerance or immunity depending on their maturation state. Previous studies have revealed that DC maturation is enhanced or accelerated upon MEK-ERK signaling pathway inhibition. We have now determined the contribution of MEK-ERK activation to the profile of gene expression of human immature monocyte-derived dendritic cells (MDDC) and peripheral blood myeloid DC. ERK inhibition altered the expression of genes that mediate CCL19-directed migration (CCR7) and LDL binding (CD36, SCARB1, OLR1, CXCL16) by immature DC. Besides, ERK upregulated CCL2 expression while impaired the expression of DC maturation markers (RUNX3, ITGB7, IDO1). MEK-ERK-regulated genes exhibited an over-representation of cognate sequences for the Aryl Hydrocarbon Receptor (AhR) transcription factor, and we show that AhR mediates some of the ERK-dependent transcriptional effects in DC. Therefore, MEK-ERK signaling pathway regulates antigen capture, lymph node homing and the acquisition of maturation-associated genes, and its contribution to the maintenance of the immature state of MDDC and myeloid DC is partly dependent on the activity of AhR. Since pharmacological modulation of the MEK-ERK signaling pathway has been proposed as a potential therapeutic strategy for cancer, our findings indicate that ERK inhibitors might influence the generation of anti-tumor responses through regulation of critical DC effector functions. Human peripheral blood monocytes from three independent healthy donors (DC4, DC5 and DC7) were isolated by anti-CD14-labeled magnetic microbeads. CD14+ monocytes were cultured for 5 days in RPMI 10% FCS containing GM-CSF and IL-4 to generate immature monocyte-derived dendritic cells (MDDC). Immature MDDC were exposed to MEK inhibitor, U0126, or p38MAPK inhibitor, SB203580 for 1 hour and a final dose of GM-CSF and IL-4 were added to the culture. Cells were collected for analysis after 4, 10 or 24 hours.Total RNA from each condition was extracted using the All prep DNA/RNA/protein mini kit (Qiagen) and hybridized to an Agilent Human Whole Genome (4x44) Oligo Microarray. All experimental procedures were performed following manufacturer instructions.

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Single cell transcriptomic profiling of human CD19+ B cells enriched for CD5+ Innate-like B cells

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