Single-cell analysis reveals multi-faceted features of B cell development, together with age-associated B cell subpopulations.
The development and maturation of B lymphocytes are critical for adaptive immunity, relying on tightly regulated gene programs within specialized microenvironments shaped by extracellular matrix and neighboring cells. However, high-dimensional, integrated analyses of B cell heterogeneity, gene regulation, and external factors during development remain limited. Here, we analyze single-cell transcriptomic and B cell receptor (BCR) sequencing data from B cells and surrounding cells in bone marrow, tonsil, and peripheral blood. We reveal the dynamics of gene regulation, the heterogeneity of conventional B cells, and stage-specific cell-cell interactions along B cell development. Immature B cells display minimal transcriptional activity and low RNA velocity, whereas naïve B cell proliferation and activation are niche-confined and individualized. Two models for memory B cell subpopulation development appear compatible and warrant further study. Cell-cell interaction analysis highlights the role of myeloid cells and identifies TNF and adhesion signaling as dominant, stage-dependent pathways. Additionally, we identify two age-associated B cell subpopulations expressing S100A8/A9 and C1q, and experimentally confirm S100A8/A9 secretion from human B cells, indicating a senescence-associated secretory phenotype. This integrated analysis provides a comprehensive resource for understanding B cell development, gene regulation, and intercellular communication, offering insights into immune aging and potential therapeutic strategies.
Authors
Yang Yang, Tang Tang, Lan Lan, He He, Chen Chen, Zeng Zeng, Liu Liu, Wu Wu, Wang Wang, Zhang Zhang
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