Immune System Organization is Encoded in Transcription

The immune system consists of diverse cell types that act in coordination, yet it remains unclear at what biological scale coherent immune organization emerges. Here we analyze single-cell transcriptomics from a large longitudinal cohort of healthy adults and demonstrate that transcription is coordinated across immune cells. Although baseline expression differs by cell type, transcriptional deviations spanning thousands of genes align across immune cells within donors. This alignment resolves into axes of transcriptional variation that organize both inter-donor differences and longitudinal change. Leading axes capture the largest fraction of variance and reflect dynamic shifts shared across donors, whereas higher-order axes encode more stable donor-specific structure. We refer to this shared multi-dimensional variance structure as the immune transcriptional landscape (ITL). An individuals position within the ITL reflects their transcriptional configuration and is recapitulated in matched serum proteomics, linking immune cell transcription to the circulating proteome. Together, these findings demonstrate that coherent immune organization is encoded in coordinated gene expression across immune cells, revealing a multi-dimensional, temporally stratified transcriptional landscape shared across individuals and over time.