Follicular dendritic cells restrict IL4 availability in germinal centers and foster memory B cell generation
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ABSTRACT:
PROVIDER: PRJNA750102 | ENA |
REPOSITORIES: ENA
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Project description:Germinal centers (GCs) are sites of antibody affinity maturation and memory B cell generation. Follicular dendritic cells (FDCs) form a dense stromal network within GCs, but the full extent of their supportive activity is not understood. Here we showed that FDCs expressed IL4Ra and they reduced IL4 availability in GCs. We used scRNA-seq to examine IL4 actions within the GC and identified a subset of light zone cells marked by high IL4Ra and CD23 and lack of a Myc gene-expression signature. Trajectory inference analysis suggested this population could differentiate into pre-memory and pre-plasma cells. Genetic experiments showed that IL4Ra and STAT6 acted intrinsically to restrain pre-memory B cell generation. By reducing IL4 availability, FDCs enhanced GC B cell selection and fostered memory cell generation. This work suggests that GC FDCs provide a niche that limits bystander IL4 activity, focusing IL4 action on B cells undergoing selection and enhancing memory cell differentiation
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Project description:Purpose: The goalsof this study was to compare the transcriptome profiling of dorsal root ganglia (DRG) of animals injected intrathecally with IL4-10 FP, the combination of IL4+IL10 or vehicle, one week after induction of persistent inflammatory pain. Methods: Mice received an intraplantar injection of carrageenan and one week developing inflammatory pain were intrathecally injected with IL4-10 FP, IL4+IL10 or PBS. DRGs were isolated and RNA libraries were prepared with the poly A selection method followed by multiplexing and sequencing on the Illumina NextSeq500® platform in a 1 × 75bp single-read and 350 million reads per lane (Utrecht Sequencing Facility) Results: In vivo IL4-10 FP induces a differential transcriptome than the combination of cytokines in mice with persistent inflammatory pain. Conclusions: The superior analgesic effect observed in mice treated with IL4-10 FP compared to mice injected with the naïve cytokines is derived from an induction of a different transcriptome on the lumbar DRGs.
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